L-SELECTIN-MEDIATED LYMPHOCYTE ROLLING OF JURKAT T-LYMPHOCYTES DEPENDS ON FUNCTIONAL EXPRESSION OF THE TYROSINE KINASE P56LCK

Selectin-mediated rolling of leukocytes on endothelial cells is the fi rst step in the recruitment of leukocytes to sites of inflammation and seems to be a necessary prerequisite for beta(2)-integrin-mediated le ukocyte sticking. The transient interaction of L-selectin expressed on leukocytes with its ligands on endothelial cells is mediated via the Ca2+-dependent lectin domain, which recognizes sialyl-Lewis(x) structu res. Deletion of the intracytoplasmic domain abolishes leukocyte rolli ng in spite of intact ligand recognition, pointing to a crucial functi on of the intracytoplasmic tail for the process of rolling. In additio n, we have previously demonstrated that I, selectin triggering leads t o intracellular activation of the Ras pathway, and this activation was dependent on the function of p56lck. In the present study, we used a fucoidan-coated flow channel to analyze the significance of intracellu lar signaling molecules for L-selectin-mediated rolling of Jurkat T ce lls. Jurkat cells, genetically deficient in p561ck (JCaM1.6), exhibite d a significant reduction of rolling compared to normal Jurkat or p56l ck-reconstituted JCaM1.6 cells. The data indicate that L-selectin-medi ated rolling depends on functional expression of the p56lck kinase.