Endothelial nitric oxide synthase regulates T cell receptor signaling at the immunological synapse
Por:
Ibiza, S, Victor, V, Bosca, I, Ortega, A, Urzainqui, A, O'Connor, J, Sanchez-Madrid, F, Esplugues, J and Serrador, J
Publicada:
1 jun 2006
Resumen:
The role of nitric oxide (NO) in T cells remains controversial, and the origin and localization of endogenous NO and whether it regulates lymphocyte activation are unclear. We show here that, within minutes of binding to antigen, T cells produce NO via endothelial nitric oxide synthase (eNOS). This process required increased intracellular Ca2+ and phosphoinositide3-kinase activity. Ely using an eNOS-green fluorescent fusion protein and fluorescent probes to detect NO, we show that eNOS translocates with the Golgi apparatus to the immune synapse of T helper cells engaged with antigen-presenting cells (APC), where it was fully activated. Overexpression of eNOS prevented the central coalescence of CD3 at the T cell-APC contact site, which was accompanied by increased phosphorylation of CD3 chain, ZAP-70, and extracellular signal-regulated kinases and increased IFN-gamma synthesis, but reduced production of IL-2. Therefore, eNOS-derived NO selectively potentiates T cell receptor signaling to antigen at the immunological synapse.
Filiaciones:
Univ Valencia, CNIC, Unidad Mixta, E-46010 Valencia, Spain
Univ Valencia, Unidad Cent Invest, E-46010 Valencia, Spain
Univ Autonoma Madrid, Hosp La Princesa, Serv Inmunol, E-28006 Madrid, Spain
Univ Valencia, Fac Med, Dept Bioquim & Biol Mol, E-46010 Valencia, Spain
Univ Valencia, Fac Med, Dept Farmacol, E-46010 Valencia, Spain
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