Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
J Immunol ; 188(7): 3223-36, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22387549

RESUMO

L-selectin functions as an important adhesion molecule that mediates tethering and rolling of lymphocytes by binding to high endothelial venule (HEV)-expressed ligands during recirculation. Subsequent lymphocyte arrest and transmigration require activation through binding of HEV-decorated homeostatic chemokines such as secondary lymphoid tissue chemokine (SLC; CCL21) to its counterreceptor, CCR7. Importantly, L-selectin also functions as a signaling molecule. In this study, signaling induced by ligation of L-selectin using mAb or endothelial cell-expressed ligand significantly enhanced the chemotaxis of murine T cells and B cells to SLC but not to other homeostatic chemokines. Consistent with the expression levels of L-selectin in different lymphocyte subsets, L-selectin-mediated enhancement of chemotaxis to SLC was observed for all naive lymphocytes and effector/memory CD8(+) T cells, whereas only a subpopulation of effector/memory CD4(+) T cells responded. During in vivo mesenteric lymph node migration assays, the absence of L-selectin on lymphocytes significantly attenuated both their ability to migrate out of the HEV and their chemotaxis away from the vessel wall. Notably, ligation of L-selectin and/or CCR7 did not result in increased CCR7 expression levels, internalization, or re-expression. Pharmacologic inhibitor studies showed that L-selectin-mediated enhanced chemotaxis to SLC required intact intracellular kinase function. Furthermore, treatment of lymphocytes with the spleen tyrosine kinase family inhibitor piceatannol reduced their ability to migrate across the HEV in peripheral lymph nodes. Therefore, these results suggest that "cross-talk" in the signaling pathways initiated by L-selectin and CCR7 provides a novel mechanism for functional synergy between these two molecules during lymphocyte migration.


Assuntos
Quimiocina CCL21/fisiologia , Quimiotaxia de Leucócito/fisiologia , Selectina L/fisiologia , Subpopulações de Linfócitos T/citologia , Animais , Anticorpos Monoclonais/farmacologia , Células Cultivadas/citologia , Células Cultivadas/efeitos dos fármacos , Células Endoteliais/citologia , Memória Imunológica , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Selectina L/genética , Selectina L/imunologia , Linfonodos/citologia , Mesentério/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/fisiologia , Receptores CCR7/biossíntese , Receptores CCR7/genética , Receptores CCR7/fisiologia , Receptores CXCR4/biossíntese , Receptores CXCR4/genética , Transdução de Sinais , Organismos Livres de Patógenos Específicos , Estilbenos/farmacologia , Quinase Syk
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA