TY - JOUR
T1 - Salicylates inhibit T cell adhesion on endothelium under nonstatic conditions
T2 - Induction of L-selectin shedding by a tyrosine kinase-dependent mechanism
AU - Gerli, R.
AU - Gresele, P.
AU - Bistoni, O.
AU - Paolucci, C.
AU - Lanfrancone, L.
AU - Fiorucci, S.
AU - Muscat, C.
AU - Costantini, V.
PY - 2001/1/15
Y1 - 2001/1/15
N2 - Salicylates inhibit T cell adhesion to and transmigration through endothelium by preventing integrin activation induced by contact with endothelial cells. In the present study the effects of aspirin and sodium salicylate on the first steps of T cell adhesion have been analyzed in a nonstatic in vitro system. Salicylates partially reduced adhesion to activated endothelium and, in parallel, L-selectin expression on resting T cells by inducing shedding of the molecule without affecting its mRNA transcript. The role of L-selectin down-regulation in reducing T cell adhesion in this system was supported by the fact that aspirin inhibited T cell adhesion also on plastic-immobilized L-selectin ligand or when α4 integrin-mediated adhesion to endothelium was blocked by specie mAbs. In addition, preincubation of T cells with inhibitors of L-selectin shedding prevented both functional and phenotypic inhibitory effects of salicylates. The decrease in T cell adhesion and L-selectin expression seems to be dependent on intracellular calcium increase and tyrosine kinase activation, because these effects could be reversed by preincubating salicylate-treated T cells with EGTA, genistein, or tyrphostin. Finally, the infusion of aspirin into healthy volunteers induced down-regulation of L-selectin on circulating T cells. These results suggest that salicylates interfere not only with integrin activation, but also with the L-selectin-mediated first steps of T cell binding to endothelium.
AB - Salicylates inhibit T cell adhesion to and transmigration through endothelium by preventing integrin activation induced by contact with endothelial cells. In the present study the effects of aspirin and sodium salicylate on the first steps of T cell adhesion have been analyzed in a nonstatic in vitro system. Salicylates partially reduced adhesion to activated endothelium and, in parallel, L-selectin expression on resting T cells by inducing shedding of the molecule without affecting its mRNA transcript. The role of L-selectin down-regulation in reducing T cell adhesion in this system was supported by the fact that aspirin inhibited T cell adhesion also on plastic-immobilized L-selectin ligand or when α4 integrin-mediated adhesion to endothelium was blocked by specie mAbs. In addition, preincubation of T cells with inhibitors of L-selectin shedding prevented both functional and phenotypic inhibitory effects of salicylates. The decrease in T cell adhesion and L-selectin expression seems to be dependent on intracellular calcium increase and tyrosine kinase activation, because these effects could be reversed by preincubating salicylate-treated T cells with EGTA, genistein, or tyrphostin. Finally, the infusion of aspirin into healthy volunteers induced down-regulation of L-selectin on circulating T cells. These results suggest that salicylates interfere not only with integrin activation, but also with the L-selectin-mediated first steps of T cell binding to endothelium.
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M3 - Article
C2 - 11145657
AN - SCOPUS:0035863729
VL - 166
SP - 832
EP - 840
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -