Assuntos
Artrite Reumatoide , Colina , Glucose , Espectroscopia de Ressonância Magnética/métodos , Osteoartrite/diagnóstico , Membrana Sinovial , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Colina/análise , Colina/metabolismo , Cromatografia por Troca Iônica/métodos , Diagnóstico Diferencial , Feminino , Glucose/análise , Glucose/metabolismo , Humanos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Medição de Risco , Líquido Sinovial/metabolismo , Membrana Sinovial/metabolismo , Membrana Sinovial/patologiaRESUMO
Eph receptors and ephrin ligands have been shown to be differentially expressed on leucocytes. Here, we show that one member of the ephrin-B subfamily of ephrins, ephrin-B3, specifically binds to B lymphocytes in blood. No binding was observed to T lymphocytes or monocytes. The ephrin-B3 binding receptor on B lymphocytes is so far not identified, but our results here indicate that ephrin-B3 binds to a protein not belonging to the Eph receptor family. Recently, we have shown that ephrin-B3 binds to a sulphated cell surface receptor on HEK293T cells and that this binding can be blocked with heparin. Ephrin-B3 binding to B lymphocytes is partially affected by heparin, and a basic amino acid in the extracellular juxtamembrane region, Arg-188, is here shown to be involved in this binding. The functional consequence of ephrin-B3 binding to B lymphocytes is induced migration, in particular of the memory cells. To conclude, ephrin-B3 binds to B lymphocytes, most likely via a non-classical receptor, and induces migration of the memory B cell subpopulation.
Assuntos
Linfócitos B/imunologia , Movimento Celular/imunologia , Efrina-B3/imunologia , Células HEK293 , Heparina/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Receptores de Superfície Celular/imunologiaRESUMO
We have demonstrated previously that binding of ephrin-A1 to EphA receptors on human CD4(+) and CD8(+) T cells stimulates migration. Two EphA receptors have been reported in T cells: EphA1 at the protein level and EphA4 at the mRNA level. In this study, we wanted to investigate the expression profile of these receptors in T cell subpopulations and to test if expression differences would affect the potential of cells to migrate upon ephrin-A1 binding. We have generated an anti-EphA4 mAb for expression analysis. Our data show that functional EphA4 is expressed on the cell surface of CD4(+) and CD8(+) T cells. In addition, EphA4 receptor expression is induced after overnight incubation in serum-free medium, in particular, on CD4(+)CD45RO(+) T cells. Migration of CD4(+) T cells in response to ephrin-A1 is observed for memory cells (CD45RO(+)) and much weaker for naïve cells (CD45RA(+)). A signaling complex associated with the EphA4 receptor has also been isolated and includes EphA1, the Src family kinases Fyn and Lck, Slp76, and Vav1. To conclude, T cells express EphA1 and EphA4 receptors. Expression differences of EphA4 are observed in subpopulations of CD4(+) T cells. This is related to the cell migration potential after ephrin-A1 binding.
