Assuntos
Antígeno CD11a/sangue , Antígenos CD18/sangue , COVID-19/imunologia , Leucócitos/metabolismo , Síndrome de Linfonodos Mucocutâneos/imunologia , Receptores de IgG/sangue , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Biomarcadores/sangue , COVID-19/sangue , COVID-19/diagnóstico , Teste para COVID-19 , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnósticoRESUMO
OBJECTIVES: Single nucleotide polymorphisms of CD11a and CD11c have been suggested as susceptibility loci in Korean patients with Behçet's disease (BD). As immunoregulatory roles of CD11c+CD8+T cells were previously observed in multiple autoimmune and autoinflammatory diseases, we aimed to investigate CD11a and CD11c in CD4+ and CD8+ subpopulation of BD patients. METHODS: Peripheral-blood mononuclear cells were isolated from 21 patients with active BD, 26 patients with inactive BD, 20 patients with recurrent aphthous ulcers (RAU), and 23 healthy controls (HCs). The surface expression of CD11a and CD11c in CD4+ and CD8+ cell populations was analyzed by flow cytometry, and CD11a and CD11c mRNA and protein levels from puri ed CD8(+) T cells were analyzed using real-time polymerase chain reaction and western blot. RESULTS: The frequencies of CD11a+ and CD11c+ cells were significantly increased in the CD4+ and CD8+ cell populations of active-BD patients, respectively, than that in the HCs. Additionally, both CD11a and CD11c mRNA and protein levels were significantly elevated in the CD8+ T cells of active-BD patients than that in the HCs. CONCLUSIONS: The CD8+ T cells of BD patients exhibited increased CD11c expression levels. Upregulation of CD11c in CD8+ cells may contribute to BD pathogenesis.
Assuntos
Síndrome de Behçet/imunologia , Antígeno CD11c/sangue , Linfócitos T CD8-Positivos/imunologia , Adulto , Síndrome de Behçet/sangue , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/genética , Biomarcadores/sangue , Western Blotting , Antígeno CD11a/sangue , Antígeno CD11c/genética , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , RNA Mensageiro/sangue , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Indução de Remissão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para CimaRESUMO
Recent research demonstrates that the underlying mechanism in immune thrombocytopenia (ITP) is very complex. Lymphocyte function associated antigen-1 (LFA-1) plays important roles in autoimmune diseases. The purpose of this study was to investigate the expression of CD11a on lymphocytes and explore its possible role in ITP. The expression of CD11a on lymphocyte subpopulations (CD3(+) T cells, CD3(+)CD4(+) T cells, CD3(+)CD4(-) T cells, CD4(+)Foxp3(+) T regulatory cells and CD19(+) B cells) were analyzed by flow cytometry. Specific anti-platelet GPIIb/IIIa and/or GPIb/IX autoantibodies were assayed by modified monoclonal antibody specific immobilization of platelet antigens (MAIPA). The mean fluorescence intensity of CD11a on CD3(+) T, CD3(+)CD4(-) T and CD19(+) B lymphocytes were increased in ITP patients compared to healthy controls. No significant difference of CD11a expression on CD3(+)CD4(+) T cells or CD4(+)Foxp3(+) T regulatory cells was found between ITP patients and controls. Our data indicates the possible role of CD11a in the pathogenesis of ITP.
Assuntos
Subpopulações de Linfócitos B/metabolismo , Antígeno CD11a/metabolismo , Púrpura Trombocitopênica Idiopática/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Antígenos CD19/metabolismo , Autoanticorpos/imunologia , Subpopulações de Linfócitos B/imunologia , Biomarcadores/metabolismo , Antígeno CD11a/sangue , Antígeno CD11a/imunologia , Complexo CD3/metabolismo , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Fenótipo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/imunologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/imunologia , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/imunologia , Linfócitos T Reguladores/imunologia , Adulto JovemRESUMO
PURPOSE: Our study tested the hypothesis that sodium (Na)-selenite expression treatment can reduce oxidative stress and increase plasma antioxidants, whereas modulating white blood cell antigen expression in severe sepsis. Selenite is a well known cofactor of glutathione peroxidases and other antioxidant enzymes; therefore, one may expect an antioxidant effect of treatment. MATERIALS: We randomized 40 severe septic patients into treatment and control groups. Treatment group (n = 21) received 1000-µg/2 hours Na-selenite load, followed by a 1000-µg/die medication. Oxidative stress markers, including malondialdehyde, maximal free radical production, and plasma antioxidants: free sulfhydryl groups, glutathione levels, and superoxide dismutase and catalase enzyme activity were measured. RESULTS: According to our results, the treatment regime successfully restored serum selenium levels. Treatment group developed a significant malondialdehyde increase by the fifth study day, whereas reactive oxygen species production decreased significantly. Reduced glutathione and plasma sulfhydryl groups showed no significant difference. Treatment group showed deteriorated expression of CD11a and slight increase of CD49d expression on monocytes throughout our study. CONCLUSIONS: Although our Na-selenite treatment regime successfully restored the selenium deficiency of severe septic patients, antioxidant and white blood cell antigen expression modulating effect of the therapy was not observed in our patient group.
Assuntos
Antioxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Sepse/tratamento farmacológico , Selenito de Sódio/uso terapêutico , Oligoelementos/uso terapêutico , Idoso , Antígeno CD11a/sangue , Catalase/sangue , Feminino , Glutationa/sangue , Glutationa Peroxidase , Humanos , Integrina alfa4/sangue , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Monócitos/imunologia , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Selênio/sangue , Sepse/sangue , Superóxido Dismutase/sangueRESUMO
OBJECTIVE: To determine the long-term effect of natalizumab (NTZ) treatment on the expression of integrins and chemokine receptors involved in the migration of T cells towards the central nervous system (CNS). METHODS: We drew the blood of 23 patients just before starting NTZ therapy and every 12 months thereafter, for up to 48 months of treatment. We assessed the ex-vivo expression of phenotype markers (CCR7 and CD45RA), CNS-addressing integrins (CD11a, CD49d and CD29) and chemokine receptors (CXCR3 and CCR6) in CD4+ or CD8+ T-cell subsets by flow cytometry. RESULTS: As compared to the pre-NTZ values, there was a marked increase in central memory (CCR7+/CD45RA-) CD4+ T cells and in effector memory (CCR7-/CD45RA-) CD8+ T cells at 12 and 24 months. In addition to an expected downregulation of both VLA-4 subunits (CD49d/CD29), we also found decreased T-cell expression of CXCR3 at 12 months, and of CD11a (LFA-1 αL subunit) at 12 months, but mostly at 24 months of NTZ treatment. CONCLUSION: Our data show a nadir of CD11a expression at 2 years of NTZ treatment, at the peak of incidence of progressive multifocal leukoencephalopathy (PML), indirectly suggesting that a lack of these molecules may play a role in the onset of PML in NTZ-treated patients.
Assuntos
Antígeno CD11a/sangue , Quimiotaxia de Leucócito/efeitos dos fármacos , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Antígeno CD11a/imunologia , Feminino , Citometria de Fluxo , Humanos , Imunossupressores/efeitos adversos , Integrina alfa4beta1/sangue , Integrina alfa4beta1/imunologia , Leucoencefalopatia Multifocal Progressiva/sangue , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/imunologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/imunologia , Natalizumab/efeitos adversos , Receptores CCR6/sangue , Receptores CCR6/imunologia , Receptores CXCR3/sangue , Receptores CXCR3/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: To determine the effect of arterial blood pressure (BP) reduction on endocan and soluble cell adhesion molecules' (sCAM) plasma concentration and expression of their ligands on circulatory leukocyte subpopulations. METHODS: 24 hypertensive subjects of both sexes (age: 53±8 yrs) were treated with Ca-channel blocker, amlodipin (5-10 mg/day for 8 weeks; to reach BP≤139/89mmHg). The serum sCAMs and endocan concentrations were determined by ELISA kits. Level of ICAM/VCAM ligands on leukocytes was assessed by flow cytometry. Paired t-test, or t-test were used as appropriate, with Pearson's correlation calculated; p<0.05 was considered significant (SigmaPlot v.11). RESULTS: sICAM-1 and sVCAM-1 were decreased (p≤0.001 and p=0.002, respectively), while E-selectin concentration was increased after amlodipin treatment (P=0.014). CD11a/LFA-1 (ICAM-1 and endocan ligand) was significantly increased in all three cell types with BP decrease. CD15 and CD49d/VLA-4 (VCAM-1 ligand) did not change after the treatment. There was significant positive correlation of systolic and diastolic BP with ICAM-1 and VCAM-1, and significant negative correlation of systolic BP with CD11a/LFA-1. Endocan significantly positively correlated with ICAM-1. CONCLUSIONS: The increased expression of ICAM/VACM ligands, together with decrease of sCAMs and endocan suggests the de-activation of endothelium with reduction in BP, decreasing the adherence of circulatory leukocytes to endothelium; subsequently decreasing the risk for development of atherosclerosis.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Moléculas de Adesão Celular/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Proteínas de Neoplasias/metabolismo , Proteoglicanas/metabolismo , Antígeno CD11a/sangue , Selectina E/sangue , Endotélio/metabolismo , Feminino , Citometria de Fluxo , Humanos , Integrina alfa4/sangue , Molécula 1 de Adesão Intercelular/sangue , Contagem de Leucócitos , Leucócitos/metabolismo , Antígenos CD15/sangue , Ligantes , Masculino , Pessoa de Meia-Idade , Tamanho da Amostra , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
BACKGROUND: The classification of acute myeloid leukemia (AML) FAB subtype M7 relies on immunophenotypic assessment. CD41 is expressed throughout all stages of maturation of megakaryocytes and has therefore been described as a specific blast cell marker in AML M7 as well as in transient myeloproliferative disease (TMD) of patients with Down syndrome (DS). However, technical difficulties underlie the need for new markers for these entities. METHODS: We evaluated the expression of human lymphocyte function-associated antigen 1 (CD11a) in a large cohort of pediatric AML and TMD patients (n = 91) of the Austrian AML-BFM 98 and 2004 studies. RESULTS: We found a consistent deficiency of CD11a as assessed by mean fluorescence intensity in all patients with non-DS AML M7 (n = 8) and M6 (n = 1), all cases of classical DS-AML (n = 12) as well as TMD (n = 15) that was statistically significant in comparison to non-DS AML M0-M5 patients (n = 55; P < 0.001, sensitivity 100%). Only three of 55 Non-DS M0-5 patients were CD11a deficient (specificity 95%). Monocytic leukemias (M4/5) and normal monocytes typically showed a high CD11a expression, FAB types M1/2 and normal neutrophils an intermediate expression level, while all M3 leukemias were rather low in CD11a expression. CONCLUSIONS: We conclude, that deficiency of CD11a expression should be added to the diagnostic criteria of AML-M7, classical DS-AML and TMD.
Assuntos
Antígeno CD11a/genética , Síndrome de Down/genética , Leucemia Megacarioblástica Aguda/genética , Transtornos Mieloproliferativos/genética , Biomarcadores/sangue , Células da Medula Óssea/patologia , Antígeno CD11a/sangue , Antígeno CD11a/metabolismo , Pré-Escolar , Síndrome de Down/sangue , Síndrome de Down/complicações , Síndrome de Down/patologia , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica , Humanos , Lactente , Recém-Nascido , Leucemia Megacarioblástica Aguda/sangue , Leucemia Megacarioblástica Aguda/complicações , Leucemia Megacarioblástica Aguda/patologia , Masculino , Monócitos/metabolismo , Monócitos/patologia , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/patologiaRESUMO
High-fat meals promote transient increases in proatherogenic factors, implicating the postprandial state in cardiovascular disease (CVD) progression. Although low-grade inflammation is associated with CVD, little research has assessed postprandial inflammation. Because of its anti-inflammatory properties, premeal exercise may counteract postprandial inflammation. The purpose of this study was to determine postprandial alterations in monocytes and circulating markers of endothelial stress and inflammation following a high-fat meal in young adults with or without premeal cycle exercise. Each subject completed two trials and was randomized to rest or cycle at a moderate intensity prior to eating a high-fat meal. Flow cytometry was used to assess monocyte cell surface receptor expression and concentration of endothelial microparticles (EMP). Plasma cytokines were assessed using Luminex MagPix. Statistical analysis was completed using separate linear mixed models analyses with first-order autoregressive (AR(1)) heterogeneous covariance structure. Significance was set at P ≤ 0.05. Percentage increases in classic monocyte CD11a and CD18 were greater overall in the postprandial period in the meal-only condition compared with the meal + exercise condition (P < 0.05). EMP concentration was 47% greater 3 h after the meal compared with premeal values in the meal-only condition (P < 0.05); no significant increase was observed in the meal + exercise condition. Premeal cycling blunted postprandial increases in EMP and CD11a and CD18. Acute, moderate-intensity exercise may help counteract possibly deleterious postprandial monocyte and endothelial cell activation.
Assuntos
Ciclismo , Antígeno CD11a/sangue , Antígenos CD18/sangue , Gorduras na Dieta/sangue , Esforço Físico , Período Pós-Prandial , Adulto , Antígenos de Superfície/sangue , Biomarcadores/sangue , Micropartículas Derivadas de Células , Endotélio Vascular , Feminino , Citometria de Fluxo , Humanos , Inflamação/sangue , Masculino , Monócitos , Adulto JovemRESUMO
INTRODUCTION: CD70 and CD11a are co-stimulatory molecules that are important for the immune functions of T, B lymphocytes. Over-expressions of CD70 or CD11a cause T cell to be autoreactive. OBJECTIVES: The purpose of this study was to explore the effect of CD70 and CD11a in immune thrombocytopenia (ITP). METHODS: CD70 and CD11a mRNAs and protein expressions in CD4(+) T cells from ITP patients were measured respectively by real-time quantitative-PCR (RT-PCR) and flow cytometry. The apoptosis of T cells, B cells, and platelets in the PBMCs were analyzed by flow cytometry, and secretion of IL-4, IFN-γ, as well as IgG in the reaction supernatant were detected by ELISA. In order to investigate the effects of CD70 and CD11a over-expression on pathogenesis of ITP, anti-CD70, and anti-CD11a mAbs were used to block the signaling pathways. RESULTS: CD70 and CD11a mRNAs and protein expressions in CD4(+) T cells from ITP patients were significantly higher than healthy controls. In vitro co-culturing of PBMCs with anti-CD70 or anti-CD11a, the apoptosis of T, B lymphocytes were significantly increased but apoptosis of platelets were reduced. Anti-CD11a and anti-CD70 both significantly suppressed the secretion of IFN-γ, while anti-CD11a significantly promoted the secretion of IL-4. There was no significant difference in the healthy group. CONCLUSIONS: CD70 and CD11a facilitate the survival of T, B lymphocytes and indirectly enhance the destruction of platelets in ITP. Blockade of CD70 or CD11a are promising therapeutic approaches for ITP.
Assuntos
Antígeno CD11a/sangue , Antígeno CD11a/imunologia , Ligante CD27/sangue , Ligante CD27/imunologia , Trombocitopenia/imunologia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais , Apoptose/imunologia , Doenças Autoimunes/terapia , Linfócitos B/metabolismo , Plaquetas/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Imunoglobulina G/biossíntese , Interferon gama/biossíntese , Interleucina-4/biossíntese , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase em Tempo Real , Trombocitopenia/metabolismo , Trombocitopenia/terapiaRESUMO
BACKGROUND AND AIMS: Approximately 50% of acute viral hepatitis in young adults and in pregnant women is due to hepatitis E virus (HEV) infection in developing countries. T cell-mediated immune injury probably plays a key role in the pathogenesis of acute hepatitis illness. However, there is a paucity of data on the global gene expression programs activated on T cells, which are subsequently responsible for T cell recruitment to the liver and triggering of immune injury. PATIENTS AND METHODS: We performed a flow cytometric analysis of T cells in individuals with acute hepatitis E (AVH-E; n=10), resolving phase of HEV (n=9), and ten healthy controls (HC). Further transcriptional profiling analysis was performed using Affymetrix GeneChip DNA microarrays to identify the genes that were differentially expressed in AVH-E and HC. RESULTS: Patients with AVH-E showed higher frequencies of CD8+ (27 ± 4%; P=0.02) and activated CD38+ CD69+ T cells (25% ± 3%; P=0.04) than in resolving phase patients (20 ± 2% and 9.1 ± 4%, respectively), who in turn exhibited higher CCR9 expression than cells from patients in active phase. The naïve T cell population (CD3+ CD45RA+) was decreased upon HEV infection (29 ± 4% in AVH-E vs. 53.1 ± 3.2% in HC; P=0.05); however, the CD11a high subpopulation within CD4+ CD45RA+ cells was increased in both AVH-E (6.1%) and resolving phase (7.7%) patients. Gene ontology analysis suggested that during AVH-E infection, there is in CD4+ T cells an activation of genes involved in pro-inflammatory responses. Additional RT-PCR analysis confirmed that in cells from AVH-E patients, there is an increased expression of CCR5, CCR9, CXCR3, CXCR4, STAT1, IRF-9, IFN-α, and TNF-α, together with a down-regulation of IL-2, SOCS3, and IL-10, with respect to cells from resolving phase patients. CONCLUSIONS: Our findings suggest the involvement of a circulating CD45RA+ CD11a high population with CCR5 expression in the pathogenesis processes of AVH-E. The obtained results help to understand the underlying inflammatory process occurring in HEV infection, which can lead to either resolution or immunopathology.
Assuntos
Antígeno CD11a/biossíntese , Convalescença , Vírus da Hepatite E/crescimento & desenvolvimento , Hepatite E , Antígenos Comuns de Leucócito/biossíntese , Receptores CCR5/biossíntese , Linfócitos T/metabolismo , Doença Aguda , Adulto , Biomarcadores/sangue , Antígeno CD11a/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Hepatite E/sangue , Hepatite E/genética , Hepatite E/imunologia , Hepatite E/virologia , Vírus da Hepatite E/imunologia , Humanos , Antígenos Comuns de Leucócito/sangue , Fígado , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Receptores CCR5/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/citologia , Linfócitos T/imunologia , Adulto JovemRESUMO
BACKGROUND: Chronic periodontitis (CP) and aggressive periodontitis (AP) are inflammatory diseases and the main cause of dental loss in adults. We aimed to investigate the expression of adhesion molecules and the source of proinflammatory and anti-inflammatory cytokines in circulating mononuclear cells from patients with CP and AP. METHODS: Peripheral blood mononuclear cells from healthy controls and CP or AP patients were collected. The expression of the cell adhesion molecules CD11a and CD11b, and the cellular sources of interleukin (IL)-4, IL-10, IL-12, interferon-γ, and tumor necrosis factor-α by distinct subpopulations of circulating leukocytes were determined using flow cytometry. RESULTS: The expression of CD11a, but not CD11b, was significantly higher within the CD4(+) and CD8(+) T cells in CP and AP than in healthy controls. The frequencies of tumor necrosis factor-α-expressing CD4(+) T cells and CD14(+) cells were higher in AP and CP, compared to healthy controls, respectively. Moreover, the frequency of IL-10 expressing CD14(+) cells was higher in CP, but not AP, compared to healthy controls CD4(+) T cells committed to IL-4 production was higher in CP than in healthy controls. CONCLUSION: These results suggest the participation of CD11a in the pathogenesis of periodontal lesions and show distinct cellular sources of immunoregulatory cytokines in AP versus CP.
Assuntos
Periodontite Agressiva/sangue , Periodontite Crônica/sangue , Citocinas/sangue , Leucócitos Mononucleares/imunologia , Adolescente , Adulto , Periodontite Agressiva/imunologia , Antígenos CD/sangue , Antígenos CD19/sangue , Antígenos de Diferenciação de Linfócitos T/sangue , Antígeno CD11a/sangue , Antígeno CD11b/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Periodontite Crônica/imunologia , Feminino , Humanos , Mediadores da Inflamação/imunologia , Molécula 1 de Adesão Intercelular/sangue , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-12/sangue , Interleucina-4/sangue , Lectinas Tipo C/sangue , Leucócitos/classificação , Receptores de Lipopolissacarídeos/sangue , Antígeno-1 Associado à Função Linfocitária/sangue , Antígeno de Macrófago 1/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Fator de Necrose Tumoral alfa/análise , Adulto JovemRESUMO
OBJECTIVES: Previous reports have shown that the depressive status in humans and experimental animals is associated with decreased immune response. Since monocyte chemotaxis and expression of CD11a are pivotal mechanisms in immune response, impairment of these events could explain the diminished immune response in depression. METHODS: To test this, rats were submitted to the forced swimming test (FST) for 3 and 15 days. Animals were sacrificed at days 4 (3 days' FST), 16 (15 days' FST) and 30 (15 days' FST and 15 days of recovery time). At these times, a blood sample was obtained for serum and leukocyte isolation. Mononuclear leukocytes were obtained by Histopaque gradient. Chemotaxis responsiveness was determined in Boyden chambers using zymosan-activated rat serum. Cellular CD11a expression and serum CD11a were determined by immunofluorescence and ELISA, respectively. RESULTS: Decreased chemotaxis was observed in FST animals at days 4 and 16 with total recovery at day 30. Diminished expression of cellular CD11a was observed at day 16 and remained decreased at day 30. There were no significant differences in serum CD11a content. CONCLUSION: Decreased chemotactic response and expression of CD11a found in this experimental model of depression could be important mechanisms to induce impairment immune response in experimental and clinical depression.
Assuntos
Antígeno CD11a/biossíntese , Quimiotaxia de Leucócito/imunologia , Tolerância Imunológica , Monócitos/imunologia , Animais , Antígeno CD11a/sangue , Antígeno CD11a/genética , Células Cultivadas , Quimiotaxia de Leucócito/genética , Transtorno Depressivo/imunologia , Transtorno Depressivo/metabolismo , Transtorno Depressivo/psicologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/imunologia , Tolerância Imunológica/genética , Imunidade Inata/genética , Masculino , Monócitos/metabolismo , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/imunologia , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Natação/psicologia , Fatores de TempoRESUMO
UNLABELLED: Acute pulmonary embolism is the third most common cause of cardiovascular mortality. Thrombolytic treatment of massive pulmonary embolism can be complicated with haemorrhage, re-thrombosis and oxidative stress. AIMS: The purpose of this study was to evaluate the changes in platelet aggregation, haemostatic, leukocyte function parameters and oxidative stress in patients with acute pulmonary embolism treated with thrombolytics. METHODS: Fifteen patients undergoing thrombolysis with ultra-high dose streptokinase ( n = 8), or alteplase ( n = 7) treatment were studied. Arterial blood samples were taken before (baseline) and after thrombolysis between the 4th and 24th hour at every four hours, on the second day twice a day and daily on the 3rd, 4th, 5th and 30th day. Platelet aggregation was examined as spontaneous and induced aggregation with adrenaline, collagen and adenosine diphosphate. D-dimer and fibrinogen were measured 8 hourly on the first day and later at the same time intervals as above. To analyse oxidative stress, blood samples were collected prior to thrombolysis, and then 8 hours, 1, 3, 5 and 30 days after treatment. Malondialdehyde, reduced glutathion, plasma sulphydryl groups levels, superoxide dismutase and myeloperoxidase enzyme activities were measured in plasma or whole blood for monitoring of the oxidative stress markers. Production of reactive oxygen species in whole blood was measured by luminol dependent chemiluminescence. Flow cytometry was used to determine CD11a, CD18, and CD97 surface antigen expression on leukocytes. RESULTS: In streptokinase group, adrenaline induced platelet aggregation decreased at the 4th and 8th hour ( p < 0.03) and was significantly lower than in the alteplase group at the 36th hour and on the 3rd day. Platelet aggregation induced by adenosine diphosphate was lower at the 4th hour than at baseline in streptokinase group ( p < 0.05). Collagen induced platelet aggregation was lower at the 4th and 8th hour than at baseline ( p < 0.05) in streptokinase group. Compared to baseline, fibrinogen levels decreased in both groups after thrombolysis. D-dimer levels elevated significantly in both therapeutic groups at the 8th hour. Spontaneous platelet aggregation was not detectable and major bleeding or re-embolism was not documented. The elevated malondialdehyde, reactive oxygen species and myeloperoxidase, decreased reduced glutathion and plasma sulphydryl levels indicated the presence of oxidative stress in patients with pulmonary embolism. Malondialdehyde significantly increased, reduced glutathion significantly decreased following thrombolysis. Reactive oxygen species production peaked on the 3rd and 5th days. Thrombolysis was accompanied by significant decrease in granulocyte and monocyte CD11a and CD18 as well as in granulocyte CD97 expression ( p < 0.05). CONCLUSION: Massive/submassive pulmonary embolism and thrombolysis injures inducible platelet aggregation. The changes in fibrinogen levels correlate significantly with the improvement of pulmonary perfusion which shows the effect of thrombolysis. Pulmonary embolism induced oxidative stress was detected on patients before thrombolysis. Thrombolytic treatment of pulmonary embolism augmented the increase of oxidative stress response and leukocyte activation following reperfusion, and these parameters normalised only on the 30th day.
Assuntos
Estresse Oxidativo/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Embolia Pulmonar/sangue , Embolia Pulmonar/tratamento farmacológico , Estreptoquinase/administração & dosagem , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Doença Aguda , Adulto , Idoso , Antígenos CD/sangue , Biomarcadores/sangue , Antígeno CD11a/sangue , Antígenos CD18/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Glutationa/sangue , Hemoglobinas/metabolismo , Hemostasia/efeitos dos fármacos , Humanos , Leucócitos/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Seleção de Pacientes , Peroxidase/sangue , Embolia Pulmonar/enzimologia , Espécies Reativas de Oxigênio/sangue , Receptores Acoplados a Proteínas G , Superóxido Dismutase/sangue , Terapia Trombolítica/métodos , Fatores de TempoRESUMO
Although it has been established that maternal leukocytes traffic from colostrum into the neonatal circulation, the effects of these cells on neonatal immunity are only beginning to be understood. This study examined the effects of maternal colostral leukocytes on development and maturation of neonatal antigen presenting cells. At birth, groups of neonatal calves received whole or cell-free colostrum (CFC) from their respective dams. Peripheral blood samples were obtained over the first 4 weeks of life, and expression of surface markers associated with cellular activation and physiological stress were monitored on monocyte lineage cells. Calves receiving cell-free colostrum at birth expressed elevated levels of CD11a, CD11c, and CD14, compared to calves receiving whole colostrum (C). Calves receiving cell-free colostrum had an elevated number of monocytes in the peripheral blood during the first 2 weeks of life, however, these cells expressed lower levels of expression of CD25 and MHC class I compared to calves receiving whole colostrum. The most significant differences in marker expression occurred within the first 7 days of life.
Assuntos
Bovinos/imunologia , Colostro/imunologia , Leucócitos Mononucleares/imunologia , Animais , Animais Recém-Nascidos , Apresentação de Antígeno , Antígeno CD11a/biossíntese , Antígeno CD11a/sangue , Antígeno CD11c/biossíntese , Antígeno CD11c/sangue , Bovinos/sangue , Linhagem da Célula/imunologia , Colostro/citologia , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Citometria de Fluxo/veterinária , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Imunoglobulina G/sangue , Imunofenotipagem/veterinária , Receptores de Lipopolissacarídeos/biossíntese , Receptores de Lipopolissacarídeos/sangue , Óxido Nítrico/biossíntese , Óxido Nítrico/sangueRESUMO
This study investigated the effect of n-3 fatty acids on adhesion molecules and tissue myeloperoxidase (MPO) activity in diabetic mice with sepsis. Diabetes was induced by a streptozotocin injection. Mice with blood glucose levels exceeding 2000 mg/l were considered diabetic. Diabetic mice were assigned to two groups with a medium-fat (10 %, w/w) diet either provided by soyabean oil (SO, n 30) or fish oil (FO, n 30). n-3 fatty acids provided 4.3 % of the total energy and the n-3/n-6 fatty acid ratio was 1:2 in the FO diet. After feeding the respective diet for 3 weeks, all mice had sepsis induced by caecal ligation and puncture (CLP) and were killed at 0, 6 or 24 h after CLP, with ten mice at each time-point. The result showed that compared with the SO group, FO group had lower PGE2 and TNF-alpha levels in peritoneal lavage fluid after CLP. Lymphocyte CD11a/CD18 expressions were higher at 6 h, whereas the percentage was lower at 24 h in the SO group than in the FO group. Neutrophil CD11b/CD18 expressions were significantly higher in the SO group than in the FO group at 0 h. The FO group had lower organ MPO activities at various time-points after CLP when compared with those of the SO group. The present findings suggest that compared with the diabetic mice fed SO, a low-dose n-3 fatty acid supplementation may attenuate leucocyte adhesion and infiltration into tissues in diabetic mice complicated with sepsis.
Assuntos
Moléculas de Adesão Celular/sangue , Diabetes Mellitus Experimental/metabolismo , Óleos de Peixe/farmacologia , Peroxidase/metabolismo , Sepse/metabolismo , Animais , Líquido Ascítico/metabolismo , Glicemia/metabolismo , Peso Corporal , Antígeno CD11a/sangue , Antígeno CD11b/sangue , Antígenos CD18/sangue , Adesão Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Suplementos Nutricionais , Dinoprostona/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Molécula 1 de Adesão Intercelular/sangue , Masculino , Camundongos , Camundongos Endogâmicos ICR , Sepse/complicações , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In hepatitis C virus (HCV) infection the immune response is ineffective, leading to chronic hepatitis and liver damage. Primed CD8 T cells are critical for antiviral immunity and subsets of circulating CD8 T cells have been defined in blood but these do not necessarily reflect the clonality or differentiation of cells within tissue. Current models divide primed CD8 T cells into effector and memory cells, further subdivided into central memory (CCR7+, L-selectin+), recirculating through lymphoid tissues and effector memory (CCR7-, L-selectin-) mediating immune response in peripheral organs. We characterized CD8 T cells derived from organ donors and patients with end-stage HCV infection to show that: 1) all liver-infiltrating CD8 T cells express high levels of CD11a, indicating the effective absence of naive CD8 T cells in the liver. 2) The liver contains distinct subsets of primed CD8+ T cells including a population of CCR7+ L-selectin- cells, which does not reflect current paradigms. The expression of CCR7 by these cells may be induced by the hepatic microenvironment to facilitate recirculation. 3) The CCR7 ligands CCL19 and CCL21 are present on lymphatic, vascular, and sinusoidal endothelium in normal liver and in patients with HCV infection. We suggest that the recirculation of CCR7+/L-selectin- intrahepatic CD8 T cells to regional lymphoid tissue will be facilitated by CCL19 and CCL21 on hepatic sinusoids and lymphatics. This centripetal pathway of migration would allow restimulation in lymph nodes, thereby promoting immune surveillance in normal liver and renewal of effector responses in chronic viral infection.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Movimento Celular/imunologia , Hepatite C Crônica/imunologia , Hepatócitos/imunologia , Memória Imunológica/imunologia , Imunofenotipagem , Receptores de Retorno de Linfócitos/biossíntese , Subpopulações de Linfócitos T/imunologia , Antígeno CD11a/biossíntese , Antígeno CD11a/sangue , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Quimiocina CCL19 , Quimiocinas CC/sangue , Quimiocinas CC/metabolismo , Criança , Hepacivirus/imunologia , Hepatite C Crônica/metabolismo , Hepatite C Crônica/patologia , Hepatócitos/citologia , Hepatócitos/patologia , Humanos , Antígenos Comuns de Leucócito/biossíntese , Antígenos Comuns de Leucócito/sangue , Ligantes , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Antígeno-1 Associado à Função Linfocitária/biossíntese , Antígeno-1 Associado à Função Linfocitária/sangue , Receptores CCR7 , Receptores CXCR4/biossíntese , Receptores CXCR4/sangue , Receptores CXCR4/metabolismo , Receptores de Quimiocinas/sangue , Receptores de Quimiocinas/metabolismo , Receptores de Retorno de Linfócitos/sangue , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/biossíntese , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangueRESUMO
An increased traffic of hematopoietic progenitor cells (HPC) between bone marrow and peripheral organs is a peculiar feature of the allergic inflammation. It has been recently reported that the sublingual form of specific immunotherapy (SLIT) is capable of reducing such an increased HPC traffic. The House Dust Mite major antigen Der p1 has been proved to up-regulate the expression of the ICAM-1 and VCAM-1 endothelial addressins, supporting the view of an inflammatory cell recruiting at the site of allergen extract administration. In the present work we have investigated, by flow-cytometric techniques, the expression of the two major integrins CD11a (LFA-1) and CD49d (VLA-4) that are the homing receptor cognate for ICAM-1 and VCAM-1 on human cord blood CD34 hematopoietic progenitor and stem cells. Even if both the investigated molecules resulted detectable on CD34+ HPC surfaces, being the system redundant, the density of the cellular expression was significantly higher for CD49d (median value: 158) than CD11a (median value: 20.5), suggesting a preferential usage of the homing axis VLA-4/VCAM-1. Results consistency with outcomes of clinical trials that relate SLIT efficacy to allergen dosage is discussed.
Assuntos
Antígeno CD11a/sangue , Dessensibilização Imunológica , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/química , Integrina alfa4/sangue , Receptores de Retorno de Linfócitos/sangue , Antígenos CD34/análise , Células da Medula Óssea/química , Células da Medula Óssea/citologia , Movimento Celular , Relação Dose-Resposta Imunológica , Citometria de Fluxo , Interações Hospedeiro-Parasita/fisiologia , Humanos , Recém-Nascido , Integrina alfa4beta1/sangue , Molécula 1 de Adesão Intercelular/metabolismo , Antígeno-1 Associado à Função Linfocitária/sangue , Pyroglyphidae/fisiologia , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
The purpose of this study was to examine the impact of intensive training for competitive sports on natural killer (NK) cell lytic activity and subset distribution. Eight female college-level volleyball players undertook 1 mo of heavy preseason training. Volleyball drills were performed 5 h/day, 6 days/wk. Morning resting blood samples were collected before training (Pre), on the 10th day of training (During), 1 day before the end of training (End), and 1 wk after intensive training had ceased (Post). CD3(-)CD16(bright)CD56(dim) (CD56(dim) NK), CD3(-)CD16(dim/-)CD56(bright) NK (CD56(bright) NK), and CD3(+)CD16(-)CD56(dim) (CD56(dim) T) cells in peripheral blood were determined by flow cytometry. The circulating count of CD56(dim) NK cells (the predominant population, with a high cytotoxicity) did not change, nor did the counts for other leukocyte subsets. However, counts for CD56(bright) NK and CD56(dim) T cells (subsets with a lower cytotoxicity) increased significantly (P < 0.01) in response to the heavy training. Overall NK cell cytotoxicity decreased from Pre to End (P = 0.002), with a return to initial values at Post. Lytic units per NK cell followed a similar pattern (P = 0.008). Circulating levels of interleukin-6, interferon-gamma, and tumor necrosis factor-alpha remained unchanged. These results suggest that heavy training can decrease total NK cell cytotoxicity as well as lytic units per NK cell. Such effects may reflect in part an increase in the proportion of circulating NK cells with a low cytotoxicity.
Assuntos
Antígeno CD56/sangue , Células Matadoras Naturais/imunologia , Esportes , Linfócitos T/imunologia , Adulto , Antígenos CD/sangue , Antígeno CD11a/sangue , Antígenos CD18/sangue , Creatina Quinase/sangue , Epinefrina/sangue , Exercício Físico , Feminino , Citometria de Fluxo , Humanos , Hidrocortisona/sangue , Contagem de Leucócitos , Ativação Linfocitária , Norepinefrina/sangueRESUMO
BACKGROUND: Cell adhesion molecules have been implicated in the adhesion of leukocytes to endothelial cells and therefore play a role in atherosclerosis, which is a frequent cause of morbidity and mortality in patients with coronary artery disease (CAD) or undergoing hemodialysis (HD). The levels of expression of leukocyte adhesion molecules were evaluated in patients with CAD or HD. METHODS AND RESULTS: The expression of leukocyte (ie, neutrophil, monocyte and lymphocyte) surface CD11a, CD18, intracellular adhesion molecule-1 (ICAM-1), very late antigen-4 alpha (VLA-4 alpha) and L-selectin was investigated by flow cytometry in 20 patients who were initially diagnosed with CAD (CAD group), 15 patients with coronary re-stenosed vessels (RESTE group), 20 undergoing HD (HD group) and 20 without CAD (CONT group). Monocyte surface expression of both CD11a and ICAM-1 in the CAD group was significantly higher than in the CONT group. Interestingly, when 15 patients with RESTE were analyzed, they showed monocyte CD11a and ICAM-1 expression levels comparable to those in the CONT group. On the other hand, there were no significant differences in the expression of CD11a, CD18, L-selectin or VLA-4 alpha between the HD group and CONT group, but monocyte L-selectin was increased in the CAD group compared with the CONT group. CONCLUSIONS: Because CD11a and CD18 are expressed on the cell surface as a heterodimer and ICAM-1 is a ligand for CD11a/CD18, this increased expression of CD11a and ICAM-1 may affect the development of initial atherosclerotic coronary stenosis, but not re-stenosis.