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1.
Adv Exp Med Biol ; 1172: 79-96, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31628652

RESUMO

The Interleukin (IL)-10 cytokine family includes IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26, which are considered as Class 2α-helical cytokines. IL-10 is the most important cytokine in suppressing pro-inflammatory responses in all kinds of autoimmune diseases and limiting excessive immune responses. Due to protein structure homology and shared usage of receptor complexes as well as downstream signaling pathway, other IL-10 family cytokines also show indispensable functions in immune regulation, tissue homeostasis, and host defense. In this review, we focus on immune functions and structures of different cytokines in this family and try to better understand how their molecular mechanisms connect to their biological functions. The molecular details regarding their actions also provide useful information in developing candidate immune therapy reagents for a variety of diseases.


Assuntos
Interleucina-10 , Doenças Autoimunes/imunologia , Humanos , Imunoterapia , Interleucina-10/química , Interleucina-10/imunologia , Transdução de Sinais/imunologia , Relação Estrutura-Atividade
2.
BMC Med Genet ; 15: 54, 2014 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-24884404

RESUMO

BACKGROUND: Rh blood group system is the most complex and immunogenetic blood group system. Prevalent RHD alleles vary in different populations. We conducted the present study to examine the genotype of DEL individuals and to elucidate whether novel alleles exist in the Chinese population. METHODS: DEL phenotype was identified by a serologic adsorption-elution method. The nucleotide sequences of ten RHD exons and exon-intron boundary regions were evaluated by RHD gene-specific PCR-SSP and sequencing. RESULTS: Of 42306 samples from individual donors and patients, 165 samples were typed as D-negative. Among these D-negative samples, 41 DEL individuals were observed. Thirty-seven DELs were confirmed to have the RHD1227A allele. Two DELs seemed to have RHD-CE-D hybrid alleles, including one RHD-CE (4-7)-D and one RHD-CE (2-5)-D. Two novel RHD alleles were found among the rest of the DEL samples, including one RHD93T > A and one RHD838G > A. CONCLUSION: In this study, about 24.85% (41/165) of the apparent D-negative Chinese individuals were DEL. RHD1227G > A is the most frequent allele in Chinese DEL phenotypes, accounting for 90.24% (37/41). The RHD-CE-D hybrid allele might be the second most frequent DEL allele in the Chinese population. Our study would contribute to the understanding of the molecular mechanism underlying D antigen expression of DEL individuals and provide useful information for designing suitable genotyping strategies in RhD-negative individuals in Asia.


Assuntos
Fenótipo , Sistema do Grupo Sanguíneo Rh-Hr/genética , Sistema do Grupo Sanguíneo Rh-Hr/metabolismo , Alelos , Éxons , Estudos de Associação Genética , Genótipo , Humanos , Íntrons , Mutação , Polimorfismo Genético , Análise de Sequência de DNA
3.
Blood Transfus ; 12(2): 244-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24333082

RESUMO

BACKGROUND: The characteristics of the D antigen are important as they influence the immunogenicity of D variant cells. Several studies on antigenic sites have been reported in normal D positive, weak D and partial D cases, including a comprehensive analysis of DEL types in Caucasians. The aim of this study was to assess D antigen density and epitopes on the erythrocyte surface of Asian type DEL phenotypic individuals carrying the RHD1227A allele in the Chinese population. MATERIALS AND METHODS: A total of 154 DEL phenotypic individuals carrying the RHD1227A allele were identified through adsorption and elution tests and polymerase chain reaction analysis with sequence-specific primers in the Chinese population. D antigen density on the erythrocyte surface of these individuals was detected using a flow cytometric method. An erythrocyte sample with known D antigen density was used as a standard. Blood samples from D-negative and D-positive individuals were used as controls. In addition, D antigen epitopes on the erythrocyte surface of DEL individuals carrying the RHD1227A allele were investigated with 18 monoclonal anti-D antibodies specific for different D antigen epitopes. RESULTS: The means of the median fluorescence intensity of D antigen on the erythrocyte membrane surface of D-negative, D-positive and DEL individuals were 2.14±0.25, 193.61±11.43 and 2.45±0.82, respectively. The DEL samples were estimated to have approximately 22 D antigens per cell. The samples from all 154 DEL individuals reacted positively with 18 monoclonal anti-D antibodies specific for different D antigen epitopes. DISCUSSION: In this study, D antigen density on the erythrocyte surface of DEL individuals carrying the RHD1227A allele was extremely low, there being only very few antigenic molecules per cell, but the D antigen epitopes were grossly complete.


Assuntos
Alelos , Epitopos/metabolismo , Eritrócitos/metabolismo , Sistema do Grupo Sanguíneo Rh-Hr/metabolismo , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Epitopos/genética , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Sistema do Grupo Sanguíneo Rh-Hr/genética
4.
Blood Transfus ; 12(2): 238-43, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23399369

RESUMO

BACKGROUND: Despite the introduction of anti-D prophylaxis into clinical practice, RhD alloimmunisation remains a problem, particularly in the context of transfusions and pregnancy-induced alloimmunisation. The incidence of RhD alloimmunisation among phenotypically RhD-negative individuals is unknown in most countries. We investigated RhD alloimmmunisation in RhD-negative pregnant women and transfusion recipients in south-east China in order to optimise the prevention of this phenomenon. METHODS: We analysed the RhD alloimmunisation status of RhD-negative pregnant women and transfusion recipients in south-east China. The RhD blood types of the study population were identified by standard serological methods. The D antigen was further tested with the indirect antiglobulin test to exclude or confirm weak D or partial D types. RhC, c, E and e antigens were typed in all subjects. If anti-D antibody screening was positive, the specificity and titre of the antibody were determined. The Del phenotype was investigated by the polymerase chain reaction sequence-specific primer method. RESULTS: An anti-D antibody was found in 61 of 416 RhD-negative pregnant women (14.66%), and in 11 of 227 RhD-negative transfusion recipients (4.85%). None of the 72 RhD-negative pregnant women or transfusion recipients with anti-D had the Del phenotype. Anti-D antibodies were not detected among Del phenotype individuals and Del phenotypes were not found in anti-D antibody producing individuals. DISCUSSION: Our study suggests that the risk of alloimmunity-induced neonatal haemolysis increases in true RhD-negative multipara. Perinatal protection would be necessary in these patients, while antenatal anti-D testing and Rh immune globulin prophylaxis would be unnecessary for RhDel pregnant women. Pregnant women and transfusion recipients with the Del type seldom produce anti-D antibody. RhD-negative recipients are not at risk of alloimmunisation after transfusion with Del red blood cells.


Assuntos
Isoanticorpos/sangue , Complicações na Gravidez , Isoimunização Rh , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Reação Transfusional , Adulto , China , Feminino , Humanos , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/prevenção & controle , Isoimunização Rh/sangue , Isoimunização Rh/epidemiologia , Isoimunização Rh/prevenção & controle , Imunoglobulina rho(D)
5.
Clin Chim Acta ; 411(7-8): 510-5, 2010 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-20064495

RESUMO

BACKGROUND: Tumstatin, an angiogenesis inhibitor with anti-tumor activity in mice, is the bioactive NC1 domain of Col IVa3, the potential significance of tumstatin as an endogenous angiogenesis inhibitor in human is not yet completely understood. This study aimed to develop an enzyme-linked immunoassay (ELISA) for tumstatin to accurately measure its concentrations in biological samples. METHODS: Recombinant tumstatin as an immunogen was expressed by E.coli. The purified tumstatin was injected into mice for antibody generation. An ELISA was developed with the monoclonal antibodies. RESULTS: The detection limit of the ELISA was 1.4ng/ml, and the intra- and inter- assay CVs were within 10%. Recovery of tumstatin added to sera was 92.7-115%. Patients with metastases had serum tumstatin levels 50% lower than patients without metastases (P=0.039). Tumstatin levels in poorly differentiated tumor tissues were significantly lower than in nontumorous tissues and well-differentiated tumor tissues (P<0.001). CONCLUSIONS: The development of a highly sensitive and reliable ELISA method capable of quantifying tumstatin in human serum samples and tissue extracts is reported. This assay for tumstatin in biological samples may be helpful in evaluating the therapeutic and/or prognostic value of tumstatin in cancer patients.


Assuntos
Autoantígenos/análise , Autoantígenos/sangue , Colágeno Tipo IV/análise , Colágeno Tipo IV/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Adulto , Idoso , Animais , Autoantígenos/isolamento & purificação , Células CHO , Colágeno Tipo IV/isolamento & purificação , Cricetinae , Cricetulus , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Proteínas Recombinantes/sangue , Proteínas Recombinantes/isolamento & purificação
6.
Clin Vaccine Immunol ; 13(2): 227-34, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16467330

RESUMO

Human nonobese diabetic-severe combined immune deficiency (NOD-SCID) mouse chimeras have been widely used as an in vivo model to assess human immune function. However, only a small fraction of transferred human T lymphocytes can be detected in human peripheral blood lymphocyte (huPBL)-NOD-SCID chimeras. To improve the reconstitution of human T lymphocytes in NOD-SCID mice, the use of recombinant human interleukin-15 (rhIL-15) as a stimulator of human lymphocytes was explored. Administration of rhIL-15 after transplantation of huPBLs into NOD-SCID mice increased reconstitution of human T lymphocytes in a dose-dependent manner, with an optimal dosage of 1 microg/mouse. The number of human T lymphocytes (HLA-ABC+ CD3+) in the lymphoid organs or tissue of rhIL-15-treated huPBL-NOD-SCID mice increased 11- to 80-fold, and phytohemagglutinin-induced T-lymphocyte proliferation and cytokine production were significantly enhanced. Additionally, although mature human cells have not been thought to enter the murine thymus, human T lymphocytes were detected in the huPBL-NOD-SCID thymus after rhIL-15 treatment. Thus, rhIL-15 can be used to optimize long-term peripheral T-cell engraftment in these human-mouse chimeras and may also be useful in clinical treatment of T-cell deficiencies.


Assuntos
Interleucina-15/farmacologia , Linfócitos T/transplante , Animais , Citocinas/biossíntese , Relação Dose-Resposta Imunológica , Facilitação Imunológica de Enxerto , Humanos , Interleucina-15/administração & dosagem , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Linfócitos T/imunologia , Quimeras de Transplante , Transplante Heterólogo
7.
Cell Mol Immunol ; 1(2): 129-36, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16212900

RESUMO

Recombinant human prolactin (rhPRL) was administered to huPBL-SCID mice to determine its effects on human immunologic reconstitution and function. The huPBL-SCID mice were given 10 microg i.p. injection of rhPRL every other day for a total of 10 injections after huPBL were transferred. The results demonstrated that rhPRL improved the engraftment of lymphocytes into thymus, lymph nodes and spleens, showing that the cellularities of these organs increased although the cellularities tended to vary depending on the donor. The amounts of human T cells (HLA-ABC+/CD3+) increased greatly in thymus (14.2 folds), spleen (4.16 folds) and lymph nodes (40.18 folds) after rhPRL injections. The amounts of human B cells (HLA-ABC+/CD19+) also increased greatly in lymph nodes (42.5 folds) and spleen (5.78 folds). The lymph node cells from the rhPRL-treated huPBL-SCID mice were more sensitive to PHA stimulation ([3H] thymidine incorporation). The supernatant of PHA-stimulated PBL from rhPRL-treated huPBL/SCID chimerism contained more cytokines (IFN-gamma and IL-2). The natural cytotoxicity against human sensitive target cells, K562 cells, from spleen and bone marrow of hPBL/SCID chimerism was significantly enhanced by rhPRL administration. The lymph node cells were stimulated with LPS in vitro for 3 days and the lymphocytes from the rhPRL-treated huPBL-SCID mice were more sensitive to mitogen stimulation. Both serum total IgG level and IgM level of rhPRL-treated huPBL/SCID chimerism were increased, and even without DT-rechallenge the base line of DT-specific IgG was elevated after rhPRL treatment in huPBL-SCID mice. Thus, rhPRL stimulation promotes reconstitution of human immune system in huPBL-SCID mice.


Assuntos
Linfócitos B/fisiologia , Linfócitos B/transplante , Prolactina/metabolismo , Linfócitos T/fisiologia , Linfócitos T/transplante , Animais , Linfócitos B/citologia , Linfócitos B/imunologia , Linhagem Celular , Quimera , Citocinas/imunologia , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/fisiologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/fisiologia , Linfonodos/citologia , Linfonodos/imunologia , Camundongos , Camundongos SCID , Prolactina/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia
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