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1.
J Periodontal Res ; 45(4): 550-6, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20412415

RESUMO

BACKGROUND AND OBJECTIVE: Inflammatory agents, such as lipopolysaccharide (LPS), in periodontal pockets may promote atherogenesis by activating leukocytes. In our previous study, we developed a microchannel chip to observe the cell adhesion process in a fluid system. The objective of this investigation was to examine the mechanism by which periodontopathic bacterial LPS enhances plaque-like formation on a microchannel chip. MATERIAL AND METHODS: To evaluate the effect of Aggregatibacter actinomycetemcomitans LPS on the expression of adhesion molecules, e.g. intercellular adhesion molecule 1 (ICAM-1), lymphocyte function-associated antigen 1 (LFA-1) and L-selectin, on the surface of murine macrophage RAW264.7 cells, the expression of each adhesion molecule was examined by flow cytometry and western blot analysis. Moreover, a flow test on the microchannel chip involving anti-adhesion molecule antibodies was conducted to clarify which adhesion molecule is related to plaque-like formation of RAW264.7 cells. RESULTS: The expressions of ICAM-1 and LFA-1 on the surface of RAW 264.7 cells increased following 12 h culture with LPS; L-selectin expression was unaffected. An increase in ICAM-1 expression was also confirmed by western blot analysis. The flow test revealed that anti-ICAM-1 antibody inhibited plaque-like formation of LPS-stimulated macrophages on the micropillars of the microchannel chip. CONCLUSION: These findings indicate that ICAM-1 plays an important role in plaque-like formation of LPS-stimulated macrophages. Our microchannel chip is a suitable tool for the investigation of etiological factors of atherosclerosis, including periodontitis, in vitro.


Assuntos
Aggregatibacter actinomycetemcomitans/fisiologia , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Selectina L/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Antígeno-1 Associado à Função Linfocitária/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Animais , Anticorpos , Aterosclerose/patologia , Western Blotting , Adesão Celular/efeitos dos fármacos , Agregação Celular/efeitos dos fármacos , Técnicas de Cultura de Células , Linhagem Celular , Citometria de Fluxo , Molécula 1 de Adesão Intercelular/análise , Selectina L/análise , Dispositivos Lab-On-A-Chip , Antígeno-1 Associado à Função Linfocitária/análise , Camundongos
2.
Respir Res ; 10: 97, 2009 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-19845971

RESUMO

BACKGROUND: Bronchus-associated lymphoid tissue (BALT) is the secondary lymphoid tissue in bronchial mucosa and is involved in the development of bronchopulmonary immune responses. Although migration of lymphocytes from blood vessels into secondary lymphoid tissues is critical for the development of appropriate adaptive immunity, the endothelia and lymphocyte adhesion molecules that recruit specific subsets of lymphocytes into human BALT are not known. The aim of this study was to determine which adhesion molecules are expressed on lymphocytes and high endothelial venules (HEVs) in human BALT. METHODS: We immunostained frozen sections of BALT from lobectomy specimens from 17 patients with lung carcinoma with a panel of monoclonal antibodies to endothelia and lymphocyte adhesion molecules. RESULTS: Sections of BALT showed B cell follicles surrounded by T cells. Most BALT CD4+ T cells had a CD45RO+ memory phenotype. Almost all BALT B cells expressed alpha4 integrin and L-selectin. In contrast, 43% of BALT T cells expressed alpha4 integrin and 20% of BALT T cells expressed L-selectin. Almost all BALT lymphocytes expressed LFA-1. HEVs, which support the migration of lymphocytes from the bloodstream into secondary lymphoid tissues, were prominent in BALT. All HEVs expressed peripheral node addressin, most HEVs expressed vascular cell adhesion molecule-1, and no HEVs expressed mucosal addressin cell adhesion molecule-1. CONCLUSION: Human BALT expresses endothelia and lymphocyte adhesion molecules that may be important in recruiting naive and memory/effector lymphocytes to BALT during protective and pathologic bronchopulmonary immune responses.


Assuntos
Brônquios/imunologia , Moléculas de Adesão Celular/análise , Neoplasias Pulmonares/imunologia , Vasos Linfáticos/imunologia , Linfócitos/imunologia , Tecido Linfoide/imunologia , Adulto , Antígenos de Superfície/análise , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Humanos , Imunidade Inata , Imunidade nas Mucosas , Imunoglobulinas/análise , Imuno-Histoquímica , Memória Imunológica , Imunofenotipagem , Integrina alfa4/análise , Selectina L/análise , Neoplasias Pulmonares/cirurgia , Antígeno-1 Associado à Função Linfocitária/análise , Proteínas de Membrana/análise , Mucoproteínas/análise , Pneumonectomia , Molécula 1 de Adesão de Célula Vascular/análise
3.
Lung ; 187(5): 331-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19672658

RESUMO

Bleomycin (BLM)-induced lung injury consists of excessive inflammatory cell infiltration and fibrosis. IS-741 has been reported to be an anti-inflammatory drug through an inhibitory action on cell adhesion. In this study we investigated whether IS-741 could inhibit the progression of pulmonary fibrosis through inflammatory cell infiltration. Lung injury was induced in female C57BL/6 mice by intratracheal instillation of BLM. IS-741 was administered daily intraperitoneally. The hydroxyproline content and fluid content in the lung on Day 28 were significantly lower in the IS-741-treated mice. The histological degree of lung injury or fibrosis was reduced in IS-741-treated mice. Administration of IS-741 caused significant reduction in the absolute number of total cells, monocyte chemoattractant protein (MCP)-1, and cysteinyl leukotriene (cysLTs) levels in bronchoalveolar lavage fluid on Day 7. Furthermore, the hydroxyproline content was significantly lower in IS-741-treated mice even though IS-741 was started on Day 14 after BLM instillation. Treatment with IS-741 had an inhibitory effect on BLM-induced lung injury and fibrosis via the repression of MCP-1 or cysLTs in this murine experimental model.


Assuntos
Anti-Inflamatórios/farmacologia , Inibidores Enzimáticos/farmacologia , Fosfolipases A2 do Grupo IV/antagonistas & inibidores , Lesão Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Fibrose Pulmonar/prevenção & controle , Piridinas/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Bleomicina , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Quimiocina CCL2/metabolismo , Cisteína/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos/administração & dosagem , Feminino , Fosfolipases A2 do Grupo IV/metabolismo , Hidroxiprolina/metabolismo , Injeções Intraperitoneais , Leucotrienos/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Antígeno-1 Associado à Função Linfocitária/análise , Camundongos , Camundongos Endogâmicos C57BL , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/prevenção & controle , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Piridinas/administração & dosagem , Índice de Gravidade de Doença , Fatores de Tempo
4.
Clin Exp Immunol ; 157(3): 377-84, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19664146

RESUMO

The cutaneous leucocyte-associated antigen receptor (CLA) can direct Leishmania-specific T lymphocytes towards inflamed skin lesions. Homing receptors [CLA, lymphocyte-associated antigen 1 (LFA-1) or CD62L] were analysed in lymphocytes from blood and cutaneous leishmaniasis (CL) lesions. CL patients with active lesions (A-CL) presented lower levels of T lymphocytes expressing the CLA(+) phenotype (T CD4(+) = 10.4% +/- 7.5% and T CD8(+) = 5.8% +/- 3.4%) than did healthy subjects (HS) (T CD4(+) = 19.3% +/- 13.1% and T CD8(+) = 21.6% +/- 8.8%), notably in T CD8(+) (P < 0.001). In clinically cured patients these percentages returned to levels observed in HS. Leishmanial antigens up-regulated CLA in T cells (CLA(+) in T CD4(+) = 33.3% +/- 14.1%; CLA(+) in T CD8(+) = 22.4% +/- 9.4%) from A-CL but not from HS. An enrichment of CLA(+) cells was observed in lesions (CLA(+) in T CD4(+) = 45.9% +/- 22.5%; CLA(+) in T CD8(+) = 46.4% +/- 16.1%) in comparison with blood (CLA(+) in T CD4(+) = 10.4% +/- 7.5%; CLA(+) in T CD8(+) = 5.8% +/- 3.4%). Conversely, LFA-1 was highly expressed in CD8(+) T cells and augmented in CD4(+) T from peripheral blood of A-CL patients. In contrast, CD62L was not affected. These results suggest that Leishmania antigens can modulate molecules responsible for migration to skin lesions, potentially influencing the cell composition of inflammatory infiltrate of leishmaniasis or even the severity of the disease.


Assuntos
Antígenos de Neoplasias/imunologia , Antígenos de Protozoários/imunologia , Leishmania braziliensis/imunologia , Leishmaniose Cutânea/imunologia , Glicoproteínas de Membrana/imunologia , Linfócitos T/imunologia , Adulto , Animais , Antígenos de Diferenciação de Linfócitos T , Antígenos de Neoplasias/análise , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , Selectina L/análise , Ativação Linfocitária , Contagem de Linfócitos , Antígeno-1 Associado à Função Linfocitária/análise , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Receptores de Retorno de Linfócitos/metabolismo , Pele/imunologia , Estatísticas não Paramétricas , Linfócitos T/metabolismo , Adulto Jovem
5.
Hepatogastroenterology ; 55(84): 836-41, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18705278

RESUMO

BACKGROUND/AIMS: The aim of the present study was to investigate the participation of the adhesion molecules and their ligands in the inflammatory process in secondary cholangitis. METHODOLOGY: Biopsy specimens were collected from the common bile duct from 29 patients with extrahepatic bile obstruction. Immunohistochemistry was used to study the expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin, LFA-1, PECAM-1, Mac-1, and VLA-4). The patients were categorized into 2 groups - chronic exacerbated cholangitis and chronic sclerotic cholangitis. RESULTS: An increased ICAM-1 expression was demonstrated and also de novo VCAM-1 and E-selectin appearance on the endothelium of microvessels in chronic exacerbated cholangitis. The inflammatory cells were strongly LFA-1-, Mac-1- positive. In chronic sclerotic cholangitis the E-selectin expression persisted on vascular endothelium in the fibrous tissue and reduced inflammatory infiltrate showed LFA-1 and VLA-4 positivity. The newly formed vessels in the fibrous connective tissue were PECAM-1-positive. CONCLUSIONS: From these results, it could be concluded that in chronic exacerbated cholangitis with complete bile obstruction the firm adhesion is mediated by ICAM-1/LFA-1 and ICAM-1/Mac-1 and less by VCAM-1/VLA-4 pathways. In chronic sclerotic cholangitis, caused by incomplete obstruction, the firm adhesion was maintained by ICAM-1/LFA-1 and less by VCAM-1/VLA-4 pathways. It seems likely that PECAM-1 and VCAM-1/VLA-4 play additional roles in neutrophil recruitment.


Assuntos
Moléculas de Adesão Celular/análise , Colangite/patologia , Colestase Extra-Hepática/patologia , Doenças do Ducto Colédoco/patologia , Adulto , Idoso , Ducto Colédoco/patologia , Selectina E/análise , Feminino , Humanos , Técnicas Imunoenzimáticas , Integrina alfa4beta1 , Molécula 1 de Adesão Intercelular/análise , Testes de Função Hepática , Antígeno-1 Associado à Função Linfocitária/análise , Antígeno de Macrófago 1/análise , Masculino , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Molécula 1 de Adesão de Célula Vascular/análise
6.
Thromb Haemost ; 96(6): 807-15, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17139377

RESUMO

Cumulative evidences have revealed that endothelial progenitor cell (EPC) transplantation can promote the neovascularization in ischemic tissue, but the mechanism of EPCs homing to the site of ischemia is poorly understood. In this study, to investigate the mechanism of human umbilical cord blood-derived high proliferative potential-endothelial progenitor cells (HPP-EPCs) homing to ischemic tissue we evaluated the expression of lymphocyte function-associated antigen-1 (LFA-1, or CD11a/CD18) and very late antigen-4 (VLA-4, or CD49d/CD29) in EPCs and the changes of expression level of their ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), in ischemic tissue and performed the adhesion and migration assays to analyze the interaction between the receptors and ligands. Furthermore, we studied the roles of LFA-1 and VLA-4 in EPC homing in an ischemic model of mice. The results show that LFA-1 andVLA-4 were expressed in HPPEPCs and ICAM-1 and VCAM-1 were expressed in vessel endothelium in ischemic tissues. The pre-incubation of HPP-EPCs with neutralizing antibodies against CD11a or CD49d reduced adhesion and migration of HPP-EPCs in vitro and reduced recovery of hind-limb blood flow, capillary density and incorporation of HPP-EPC into ischemic tissues in vivo. Furthermore, the pre-incubation of HPP-EPCs with the combination of CD11a and CD49d antibodies led to synergistically negative effects on adhesion and transmigration of HPP-EPCs in vitro, and on the homing of HPP-EPCs to ischemic tissue and on neovascularization capacity in vivo. These results indicate that LFA-1 andVLA-4 are involved in HPP-EPC homing to ischemic tissues.


Assuntos
Movimento Celular , Proliferação de Células , Células Endoteliais/imunologia , Integrina alfa4beta1/análise , Isquemia/imunologia , Antígeno-1 Associado à Função Linfocitária/análise , Músculo Esquelético/irrigação sanguínea , Células-Tronco/imunologia , Animais , Anticorpos , Antígenos CD/metabolismo , Células da Medula Óssea/imunologia , Antígeno CD11a/imunologia , Capilares/citologia , Capilares/imunologia , Adesão Celular , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Células Endoteliais/transplante , Feminino , Humanos , Integrina alfa4/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Isquemia/fisiopatologia , Isquemia/cirurgia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/metabolismo , Fluxo Sanguíneo Regional , Transplante de Células-Tronco , Células-Tronco/fisiologia , Fatores de Tempo , Molécula 1 de Adesão de Célula Vascular/metabolismo
7.
Int J Biol Markers ; 21(4): 218-22, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17177159

RESUMO

BACKGROUND/AIMS: Multiple myeloma is an incurable disease and patients eventually die of disease progression due to drug resistance. VLA-4 (very late antigen 4), VCAM (vascular adhesion molecule), LFA-1 (leukocyte function-associated antigen 1), and ICAM-1 (intercellular adhesion molecule 1)-mediated adhesion of myeloma cells to bone marrow stromal cells induces primary multidrug resistance in vitro. Based on these preclinical data we hypothesized that myeloma cells with strong adhesion - due to strong expression of adhesion molecules on the cell surface - are selected by chemotherapy in patients. To prove this hypothesis we determined the expression levels of adhesion molecules in 31 multiple myeloma patients by flow cytometry. METHODS: A 3-color stain with CD38, CD138 and antibodies against VLA-4, ICAM-1, LFA-1, and VCAM was performed. The patients were either at diagnosis (chemo-naive; n=17) or at relapse (pre-treated; n=15). Furthermore, the response to the next chemotherapy of chemo-naive patients was correlated with the expression levels of adhesion molecules. RESULTS: ICAM-1, VLA-4, and VCAM expression was higher in pre-treated patients than in chemo-naive patients and the expression levels increased with the number of chemotherapy regimens. Primarily multidrug-resistant patients had significantly higher expression levels of VLA-4 and ICAM-1 than responders. CONCLUSION: This study suggests that multiple myeloma cells expressing high levels of VLA-4 and ICAM-1 are drug resistant and that such a subpopulation of cells is selected by chemotherapy.


Assuntos
Moléculas de Adesão Celular/análise , Mieloma Múltiplo/tratamento farmacológico , ADP-Ribosil Ciclase 1/análise , Adesão Celular , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Integrina alfa4beta1/análise , Molécula 1 de Adesão Intercelular/análise , Antígeno-1 Associado à Função Linfocitária/análise , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Mieloma Múltiplo/química , Mieloma Múltiplo/patologia , Sindecana-1/análise , Molécula 1 de Adesão de Célula Vascular/análise
8.
FEBS Lett ; 580(18): 4435-42, 2006 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-16854414

RESUMO

Integrins are type I heterodimeric (alpha/beta) cell adhesion molecules. They trigger cell-signaling by recruiting cytosolic molecules to their cytoplasmic tails. Integrin alpha cytoplasmic tail contributes towards integrin function specificity, an important feature of integrins having different alpha subunits but sharing the same beta subunit. Herein, we show that the src family kinase Hck co-capped selectively with leukocyte integrin alpha(M)beta(2) but not alpha(L)beta(2) or alpha(X)beta(2). This was disrupted when the alpha(M) cytoplasmic tail was substituted with that of alpha(L) or alpha(X). Co-capping was recovered by alpha(L) or alpha(X) cytoplasmic tail truncation or forced separation of the alpha and beta cytoplasmic tails via salt-bridge disruption.


Assuntos
Antígeno de Macrófago 1/metabolismo , Proteínas Proto-Oncogênicas c-hck/metabolismo , Sequência de Aminoácidos , Animais , Adesão Celular , Linhagem Celular , Humanos , Integrina alfaXbeta2/análise , Integrina alfaXbeta2/química , Integrina alfaXbeta2/metabolismo , Antígeno-1 Associado à Função Linfocitária/análise , Antígeno-1 Associado à Função Linfocitária/química , Antígeno-1 Associado à Função Linfocitária/metabolismo , Antígeno de Macrófago 1/análise , Antígeno de Macrófago 1/química , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Fagossomos/enzimologia , Proteínas Proto-Oncogênicas c-hck/análise , Deleção de Sequência
9.
APMIS ; 114(4): 247-54, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16689823

RESUMO

Hepatitis C virus (HCV) recurrence after liver transplantation has been associated with chronic rejection. Biopsies from 10 patients with post-transplant HCV were examined for expression of adhesion molecules ICAM-1, VCAM-1, and ELAM-1, number of lymphocytes positive for their ligands LFA-1, VLA-4, and SLeX, and activation markers MHC class II antigens and IL2-R by immunohistochemistry. The phenotypes of the graft-infiltrating lymphocytes were determined. Results were compared to those for patients with normal graft function or rejection. Five recipients with HCV reactivation and one with de novo HCV had a biopsy available showing induction of ICAM-1 in sinusoidal endothelium (p<0.05) and hepatocytes (p<0.01), and Class II antigens in hepatocytes (p<0.01), compared to normal controls. Lymphocytes in the graft infiltrate expressed LFA-1, VLA-4, and Class II antigens, but IL2-R was not significantly expressed. CD3+, CD4+, and CD8+ cells were observed. In our study, HCV recurrence was not associated with acute or chronic rejection, and the inflammation was due to the viral infection.


Assuntos
Moléculas de Adesão Celular/metabolismo , Hepacivirus , Hepatite C Crônica/metabolismo , Hepatite C Crônica/patologia , Transplante de Fígado , Linfócitos/patologia , Moléculas de Adesão Celular/análise , Selectina E/análise , Selectina E/metabolismo , Feminino , Antígenos de Histocompatibilidade Classe II/análise , Humanos , Integrina alfa4beta1/análise , Molécula 1 de Adesão Intercelular/análise , Molécula 1 de Adesão Intercelular/metabolismo , Fígado/química , Fígado/patologia , Antígeno-1 Associado à Função Linfocitária/análise , Linfócitos/química , Masculino , Oligossacarídeos/análise , Receptores de Interleucina-2/análise , Recidiva , Antígeno Sialil Lewis X , Regulação para Cima , Molécula 1 de Adesão de Célula Vascular/análise , Molécula 1 de Adesão de Célula Vascular/metabolismo
10.
Virol J ; 3: 25, 2006 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-16600047

RESUMO

BACKGROUND: Primary HIV infection can develop from exposure to HIV in the oral cavity. In previous studies, we have documented rapid and extensive binding of HIV virions in seminal plasma to intact mucosal surfaces of the palatine tonsil and also found that virions readily penetrated beneath the tissue surfaces. As one approach to understand the molecular interactions that support HIV virion binding to human mucosal surfaces, we have examined the distribution of the primary HIV receptor CD4, the alternate HIV receptors heparan sulfate proteoglycan (HS) and galactosyl ceramide (GalCer) and the co-receptors CXCR4 and CCR5 in palatine tonsil. RESULTS: Only HS was widely expressed on the surface of stratified squamous epithelium. In contrast, HS, GalCer, CXCR4 and CCR5 were all expressed on the reticulated epithelium lining the tonsillar crypts. We have observed extensive variability, both across tissue sections from any tonsil and between tonsils, in the distribution of epithelial cells expressing either CXCR4 or CCR5 in the basal and suprabasal layers of stratified epithelium. The general expression patterns of CXCR4, CCR5 and HS were similar in palatine tonsil from children and adults (age range 3-20). We have also noted the presence of small clusters of lymphocytes, including CD4+ T cells within stratified epithelium and located precisely at the mucosal surfaces. CD4+ T cells in these locations would be immediately accessible to HIV virions. CONCLUSION: In total, the likelihood of oral HIV transmission will be determined by macro and micro tissue architecture, cell surface expression patterns of key molecules that may bind HIV and the specific properties of the infectious inoculum.


Assuntos
Infecções por HIV/etiologia , Doenças da Boca/etiologia , Tonsila Palatina/virologia , Receptores de HIV/análise , Células Epiteliais/química , Galactosilceramidas/análise , Proteoglicanas de Heparan Sulfato/análise , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/análise , Interleucina-8/análise , Antígeno-1 Associado à Função Linfocitária/análise , Tonsila Palatina/química , Tonsila Palatina/imunologia , Receptores CCR5/análise , Receptores CXCR4/análise , Subpopulações de Linfócitos T/imunologia
11.
Pathol Int ; 56(2): 55-61, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16445816

RESUMO

According to previous report, adhesion of CD8-positive cells and macrophages to glomerular endotherial cells through the lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) pathway is crucial for the initiation and subsequent progression of anti-glomerular basement membrane (anti-GBM) antibody-induced glomerulonephritis (anti-GBM nephritis) in WKY rats. In the present study glomerular inflammatory cell infiltration and LFA-1/ICAM-1 expression were examined in anti-GBM nephritis induced in WKY rats with monoclonal anti-GBM antibodies of different subclasses: IgG1, IgG2a, and IgG2b. The IgG2a and IgG2b subclasses induced significant proteinuria from day 3 as compared with the IgG1 subclass. Glomerular infiltration of macrophages and CD8-positive cells after administration of IgG2a and IgG2b subclass antibodies was significantly elevated compared to that for the IgG1 subclass. The intensity of glomerular ICAM-1 immunostaining by the IgG2a and IgG2b subclass antibodies tended to be stronger than that by the IgG1 subclass. Glomerular LFA-1-positive cell infiltration by the IgG2a and IgG2b subclasses was significantly higher than that of the IgG1 subclass. These results demonstrate that monoclonal antibodies belonging to the IgG2a and IgG2b subclasses strongly induce glomerular infiltration of inflammatory cells and expression of adhesion molecules in rat anti-GBM nephritis.


Assuntos
Doença Antimembrana Basal Glomerular/patologia , Molécula 1 de Adesão Intercelular/análise , Glomérulos Renais/química , Glomérulos Renais/patologia , Antígeno-1 Associado à Função Linfocitária/análise , Animais , Doença Antimembrana Basal Glomerular/imunologia , Doença Antimembrana Basal Glomerular/metabolismo , Anticorpos/imunologia , Autoanticorpos , Proliferação de Células , Feminino , Imunoglobulina G/imunologia , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/genética , Antígeno-1 Associado à Função Linfocitária/genética , Macrófagos/patologia , Ratos , Ratos Endogâmicos WKY
13.
Eur J Haematol ; 74(3): 228-40, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15693793

RESUMO

OBJECTIVES: In this study, we examined the expression of CD226 on megakaryocytic, granulocytic and erythroid lineage from hematopoietic stem cells/progenitor cells in adult and fetus and its potential role in megakaryocytic maturation. METHODS: CD34(+) cells from adult and fetus were induced to differentiate toward the megakaryocytic lineage by thrombopoietin (TPO) and the granulocytic lineage by granulocyte colony-stimulating factor (G-CSF), respectively. Mononuclear cells from fetal liver and CD34(+) cells from adult were induced to differentiate toward erythroid-lineage by erythropoiesis (EPO). We investigated the expression of CD226 and lymphocyte function associated antigen-1 (LFA-1) (CD11a) during hemopoiesis. We also studied the effect of CD226 monoclonal antibody (MoAb) and LFA-1 MoAb on megakaryocyte with antibody cross-liking technique. RESULTS: CD34(+) cells from adult and fetus and TPO-induced CD41(+) cells all expressed CD226 molecule. CD226 was not expressed on erythroid progenitor cells and erythroblasts and most cells of granulocytic lineage although G-CSF induced a significant increase of the expression of CD226 on CD34(+) cells in early period of time. CD226 MoAb acts on megakaryocytes by inducing intracellular calcium mobilization. The expression of LFA-1 decreased significantly at late stage of differentiation and maturation of fetal megakaryocytes whereas the expression of LFA-1 on adult megakaryocytes retained at a high level. CD226 MoAb in combination with LFA-1 MoAb shifted the ploidy of generated megakaryocytes from adult-derived CD34(+) cells to higher classes significantly although CD226 and LFA-1 MoAb slightly increased the ploidy of the generated megakaryocytes individually. CD226 MoAb or LFA-1 MoAb or CD226 MoAb plus LFA-1 MoAbs did not increase the ploidy of the generated megakaryocytes from fetus-derived CD34(+) cells. CONCLUSION: CD226 molecules play an important role in maturation of the megakaryocytes in combination with LFA-1.


Assuntos
Antígenos de Diferenciação de Linfócitos T/fisiologia , Células-Tronco Hematopoéticas/citologia , Antígeno-1 Associado à Função Linfocitária/fisiologia , Megacariócitos/citologia , Poliploidia , Adulto , Anticorpos Monoclonais/farmacologia , Antígenos CD34 , Antígenos de Diferenciação de Linfócitos T/análise , Antígenos de Diferenciação de Linfócitos T/imunologia , Sinalização do Cálcio/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula , Células Cultivadas , Feto , Fator Estimulador de Colônias de Granulócitos/farmacologia , Granulócitos/citologia , Humanos , Fígado/citologia , Fígado/embriologia , Antígeno-1 Associado à Função Linfocitária/análise , Antígeno-1 Associado à Função Linfocitária/imunologia , Megacariócitos/metabolismo , Trombopoetina/farmacologia
14.
Transfusion ; 44(12): 1769-73, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15584993

RESUMO

BACKGROUND: Alterations in expression of adhesion molecules are important in the trafficking of hematopoietic progenitors and probably in the mobilization process. Relatively little and conflicting data are currently available on the differences in expression between good and poor mobilizing patients. STUDY DESIGN AND METHODS: In this study, the expression of eight adhesion molecules on the collected CD34+ cells from 36 patients undergoing mobilization was determined. RESULTS: Good mobilizing patients, defined as those who collected their target in one apheresis procedure, had significantly fewer cells that expressed CD11a (LFA-1) and CD54 (ICAM-1) and borderline fewer that expressed CD11c, CD49d (VLA-4), and CD49d (VLA-5). No differences were detected in CD11b (Mac-1), CD15s (sLe(x)), or CD62L (L-selectin). Linear regression analysis identified number of prior chemotherapy courses and expression of CD11a (LFA-1) as independent predictive factors for mobilization efficiency. Good and poor mobilizing patients had approximately the same number of total CD34+ cells collected and little difference in times to engraftment. CONCLUSIONS: CD11a (LFA-1) expression inversely correlates with mobilization efficiency. Elucidation of the mechanism(s) underlying these observations will require further study.


Assuntos
Antígenos CD34/análise , Moléculas de Adesão Celular/análise , Mobilização de Células-Tronco Hematopoéticas , Adolescente , Adulto , Feminino , Humanos , Integrina alfa4beta1/análise , Integrina alfa5beta1/análise , Molécula 1 de Adesão Intercelular/análise , Antígeno-1 Associado à Função Linfocitária/análise , Masculino , Pessoa de Meia-Idade
15.
Exp Hematol ; 32(8): 728-34, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15308324

RESUMO

OBJECTIVE: A role for leukocytes in vasoocclusion is becoming increasingly recognized. Here we investigate a possible role for the eosinophil in sickle cell anemia (SCA). PATIENTS AND METHODS: Eosinophils were isolated from whole blood samples of 59 steady-state SCA homozygous SS and control individuals using Percoll gradient separation, followed by immunomagnetic sorting. Adhesion of cells to FN was evaluated using static adhesion assays (60 min, 37 degrees C, 5% CO2) and eosinophil adhesion molecular expression was observed by flow cytometry. RESULTS: SCA patients presented significantly elevated absolute eosinophil numbers. Furthermore, eosinophils isolated from these individuals demonstrated a significantly greater adhesion ( approximately 70% increased) to fibronectin (FN) than normal eosinophils in static adhesion assays. Coincubation of eosinophils with integrin-blocking monoclonal antibodies in adhesion assays showed that an association of the VLA-4, LFA-1, and Mac-1 integrins mediate the adhesion of SCA eosinophils to FN. Flow cytometry demonstrated that the expression of these integrins, however, was unaltered on the surface of SCA eosinophils, suggesting that the increased SCA eosinophil adhesion is a consequence of increased integrin affinity or avidity. SCA eosinophil adhesion to FN was further increased by the cytokine, GM-CSF, indicating that inflammation processes may further stimulate eosinophil adhesion in these patients. CONCLUSION: We report that eosinophil numbers may be significantly increased in SCA individuals and that these cells appear to exist in an activated state. Such alterations may indicate a role for the eosinophil in the vasooclusive process.


Assuntos
Anemia Falciforme/sangue , Adesão Celular , Eosinófilos/fisiologia , Adolescente , Adulto , Quimiocina CCL5/farmacologia , Criança , Feminino , Fibronectinas/fisiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Integrina alfa4beta1/análise , Interleucina-8/farmacologia , Antígeno-1 Associado à Função Linfocitária/análise , Masculino , Pessoa de Meia-Idade
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 12(2): 174-8, 2004 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-15157328

RESUMO

The objective of study was to investigate the effect of ligustrazine on the expression of LFA-1 and ICAM-1 in bone marrow and the mechanism of hematopoietic reconstitution after bone marrow transplantation (BMT). The 150 mice were randomly divided into 3 groups: normal group, saline group and ligustrazine group. The normal group was not treated. The saline group was given normal saline (0.2 ml/mouse, twice a day) through gastric tube, while the ligustrazine group was given ligustrazine (0.2 ml/mouse, twice a day) through gastric tube. At days 7, 14, 21 and 28 after BMT, the survival rate, colony forming unit of spleen (CFU-S), peripheral blood cells, bone marrow mononuclear cells (BMMNC), histologic changes of bone marrow, as well as the expression level of LFA-1 and ICAM-1 were observed. The results showed that in ligustrazine group CFU-S counts on day 10 and survival rate, WBC and Plt amount in peripheral blood, BMMNC counts, hematopoietic tissue volume as well as the expression level of LFA-1 at 7, 14, 21, 28 days after BMT were higher than in saline group (P < 0.01 or P < 0.05). However, mature RBC volume and expression level of ICAM-1 were lower than in the saline group (P < 0.01 or P < 0.05). Furthermore, fat tissue volume was higher at 7 and 14 days (P < 0.01) and was lower at 21 and 28 days (P < 0.01) after BMT than in the saline group. It is concluded that ligustrazine could improve bone marrow microenvironment and promote hematopoietic reconstitution.


Assuntos
Transplante de Medula Óssea , Molécula 1 de Adesão Intercelular/análise , Antígeno-1 Associado à Função Linfocitária/análise , Pirazinas/farmacologia , Animais , Contagem de Células Sanguíneas , Exame de Medula Óssea , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C
17.
J Anat ; 203(4): 391-404, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14620379

RESUMO

The role that pleural mesothelial cells play in leucocyte transmigration into the pleural cavity was investigated in lipopolysaccharide-stimulated mice. Changes in mesothelial cell morphology and changes in expression of adhesion molecules on mesothelial cells and leucocytes were analysed by light microscopy, immunohistochemistry, transmission electron microscopy (TEM) and immuno-scanning electron microscopy (immuno-SEM). After stimulation, the mesothelial cells separated completely from one another before leucocyte penetration across the mesothelial layer occurred. These changes occurred primarily in the immediate vicinity of ribs, where a large number of leucocytes accumulated. Immuno-SEM showed that the expression of intercellular adhesion molecule-1 (ICAM-1) on the parietal pleural mesothelial cells was significantly up-regulated by lipopolysaccharide stimulation, and that of vascular cell adhesion molecule-1 (VCAM-1) was induced. Both were restricted to the microvilli of the mesothelial cells. By contrast, expression of intercellular adhesion molecule-2 (ICAM-2), platelet/endothelial cell adhesion molecule-1 (PECAM-1), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), peripheral node addressin (PNAd) and fibronectin were not detected. Lymphocyte function associated antigen-1 (LFA-1), macrophage-1 molecule (Mac-1) and very late appearing antigen-4 (VLA-4), all ligands of ICAM-1 and VCAM-1, were present on the transmigrated neutrophils and macrophages. These findings demonstrate that the immediate vicinity of ribs is a source of leucocyte migration into the pleural space.


Assuntos
Células Epiteliais/fisiologia , Leucócitos/fisiologia , Pleura/imunologia , Animais , Antígenos de Superfície/análise , Moléculas de Adesão Celular , Movimento Celular/fisiologia , Selectina E/análise , Células Epiteliais/química , Fibronectinas/análise , Imunoglobulinas/análise , Imuno-Histoquímica/métodos , Integrina alfa4beta1/análise , Molécula 1 de Adesão Intercelular/análise , Leucócitos/química , Lipopolissacarídeos , Antígeno-1 Associado à Função Linfocitária/análise , Antígeno de Macrófago 1/análise , Masculino , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos ICR , Microscopia Imunoeletrônica , Mucoproteínas/análise , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Pleura/ultraestrutura , Organismos Livres de Patógenos Específicos , Molécula 1 de Adesão de Célula Vascular/análise
18.
Blood ; 102(1): 215-22, 2003 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-12637320

RESUMO

Many surface receptors and signaling molecules are thought to associate with unique membrane microdomains termed lipid rafts. We examined the involvement of lipid rafts in the activation of leukocyte function-associated antigen-1 (LFA-1). Depletion or sequestration of cholesterol with methyl-beta-cyclodextrin (MCD) or filipin, respectively, strongly inhibited LFA-1-mediated adhesion of T-cell lines and primary T cells. This inhibition was reversed by cholesterol reconstitution. LFA-1 on T-cell lines was detected in cold Triton X-100-insoluble lipid rafts, which were disrupted by MCD or filipin treatment. However, no LFA-1 on primary T cells was detected in lipid rafts isolated by the same procedures, and these rafts were resistant to cholesterol depletion or sequestration. Association of LFA-1 with lipid rafts of primary T cells could be detected only when they were isolated with another nonionic detergent, Brij 35. Upon treatment with MCD, LFA-1 in Brij 35-insoluble lipid rafts partially shifted to nonraft fractions. T-cell lines were found to have a high level of cholesterol and a low level of ganglioside GM1, a common marker for lipid rafts, whereas primary T cells have a much lower level of cholesterol and a very high amount of GM1. Cross-linking of LFA-1 on primary T cells induced cocapping of cholesterol but not GM1. These results suggest that lipid rafts of T cells are heterogenous, and LFA-1 associates with a subset of lipid rafts containing a high level of cholesterol. This association seems to regulate LFA-1 functions, possibly by facilitating LFA-1 clustering.


Assuntos
Colesterol/fisiologia , Antígeno-1 Associado à Função Linfocitária/fisiologia , Microdomínios da Membrana/química , Linfócitos T/ultraestrutura , beta-Ciclodextrinas , Animais , Adesão Celular , Colesterol/análise , Ciclodextrinas/farmacologia , Filipina/farmacologia , Gangliosídeo G(M1)/análise , Capeamento Imunológico , Antígeno-1 Associado à Função Linfocitária/análise , Antígeno-1 Associado à Função Linfocitária/imunologia , Microdomínios da Membrana/efeitos dos fármacos , Microdomínios da Membrana/fisiologia , Camundongos , Octoxinol , Polidocanol , Polietilenoglicóis , Linfócitos T/citologia , Linfócitos T/metabolismo , Células Tumorais Cultivadas
19.
Eur J Dermatol ; 13(6): 548-52, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14721774

RESUMO

The initial steps of melanocytic dysfunction in vitiligo are hitherto not well understood. The aim of the present study was to examine the sequence of early events that occur in melanocytes after autologous minigrafting in patients with vitiligo, depending on their clinical response. Six patients with non-segmental widespread vitiligo were included in the study. Specimens of vitiliginous lesions were used as preoperative controls and sequential punch biopsies were taken from the grafted areas on days 14, 17, 21 and 28 after minigrafting. Immunohistochemical stains using the MoAbs HMB-45, CD4, CD8, ICAM-1, and LFA-1 were performed in all biopsies and the labelled cells were counted by a digital image analyser. Results obtained show that in vitiligo patients not responding to minigrafting, significant numbers of cytotoxic T-lymphocytes and LFA-1 positive infiltrating cells occur in early phases (p < 0.05), suggesting that a cell-mediated immune response takes place towards the grafted melanocytes. Possibly this cell-mediated mechanism causing unresponsiveness to minigrafts may also play a role in the pathogenesis of vitiligo.


Assuntos
Transplante de Pele , Pele/metabolismo , Vitiligo/metabolismo , Adulto , Antígenos de Neoplasias/análise , Antígenos CD4/análise , Antígenos CD8/análise , Feminino , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/análise , Leucócitos/química , Antígeno-1 Associado à Função Linfocitária/análise , Masculino , Melanócitos/química , Antígenos Específicos de Melanoma , Proteínas de Neoplasias/análise , Pele/imunologia , Pele/patologia , Vitiligo/imunologia , Vitiligo/patologia , Vitiligo/cirurgia
20.
Blood ; 101(4): 1637-44, 2003 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-12393484

RESUMO

Relapse of B-lineage acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (HSCT) commonly results from the failure of a graft-versus-leukemia (GVL) effect to eradicate minimal residual disease. Augmenting the GVL effect by the adoptive transfer of donor-derived B-ALL-specific T-cell clones is a conceptually attractive strategy to decrease relapse rates without exacerbating graft-versus-host disease (GVHD). Toward this end, we investigated whether a genetic engineering approach could render CD8(+) cytotoxic T lymphocytes (CTLs) specific for tumor cells that express the B-cell lineage cell surface molecule CD19. This was accomplished by the genetic modification of CTLs to express a chimeric immunoreceptor composed of a CD19-specific single-chain immunoglobulin extracellular targeting domain fused to a CD3-zeta intracellular signaling domain. CD19-redirected CTL clones display potent CD19-specific lytic activity and chimeric immunoreceptor-regulated cytokine production and proliferation. Because B-ALL cells can evade T-cell/natural killer- cell recognition by down-regulation of cell surface accessory molecules that participate in the formation of a functional immunologic synapse, we compared the CD19-specific effector function of genetically modified CD8(+) CTLs toward CD19(+) cells with disparate levels of intercellular adhesion molecule 1 (ICAM-1), leukocyte function-associated antigen 1 (LFA-1), and LFA-3. We observed that recognition of B-lineage tumor lines by CD19-specific CTLs was not impaired by low levels of ICAM-1, LFA-1, and LFA-3 cell surface expression, a functional attribute that is likely a consequence of our high-affinity CD19-specific chimeric immunoreceptor. Furthermore, the CD19-specific CTLs could lyse primary B-ALL blasts. These preclinical observations form the basis for implementing clinical trials using donor-derived CD19-specific T-cell clones to treat or prevent relapse of B-ALL after allogeneic HSCT.


Assuntos
Antígenos CD19/imunologia , Linfócitos B/imunologia , Células Clonais/imunologia , Efeito Enxerto vs Leucemia/imunologia , Linfócitos T Citotóxicos/imunologia , Transferência Adotiva , Antígenos CD19/genética , Western Blotting , Linfoma de Burkitt/imunologia , Linfoma de Burkitt/terapia , Complexo CD3/genética , Complexo CD3/imunologia , Antígenos CD58/análise , Citocinas/biossíntese , Citometria de Fluxo , Expressão Gênica , Transplante de Células-Tronco Hematopoéticas , Humanos , Molécula 1 de Adesão Intercelular/análise , Ativação Linfocitária , Antígeno-1 Associado à Função Linfocitária/análise , Proteínas Recombinantes de Fusão/imunologia , Recidiva , Transdução de Sinais , Linfócitos T Citotóxicos/química , Transfecção
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