Effects of continuous exposure to stromal cell-derived factor-1 alpha on Tcell rolling and tight adhesion to monolayers of activated endothelial cells

Immobilized stromal cell-derived factor-1 alpha (SDF-1 alpha) has been show n to induce tight adhesion of T cells to purified ICAM-1 in assays done und er flow conditions. In this study, we show that soluble SDF-1 alpha induced a rapid (within 20 s) cessation of rolling and tight adhesion of >90% of t he rolling T cells on monolayers of activated endothelial cells under simil ar flow. Within 4 min, the T cells had either started to migrate between th e endothelial cells or re-entered the rolling and circulating lymphocyte po ol. This deadherence of the firmly bound cells, with either ensuing transmi gration or continued rolling, was most likely due to desensitization of lym phocytes to the continuously present SDF-1 alpha. The released rolling lymp hocytes could still respond to other activating signals by a second round o f tight adhesion. Pretreating the lymphocytes with pertussis toxin almost c ompletely blocked the effect of the chemokine, confirming that the inductio n of firm adhesion was due to the function of the chemokine on the lymphocy tes and not the endothelial cells. Pretreating the endothelium with SDF-1 a lpha did not lead to firm adhesion of subsequently added lymphocytes, also indicating that the effect was due to soluble, not endothelially bound, che mokine, Blocking experiments showed that the same molecules mediated rollin g before and after SDF-1 alpha-induced tight adhesion. This is the first st udy to demonstrate the effect of soluble SDF-1 alpha on T cell rolling on a n endothelial cell monolayer, The data broaden our understanding of the sti mulatory factors directing the firm adhesion and ensuing transmigration of leukocytes into tissues through activated endothelium.