L-SELECTIN REGULATES ACTIN POLYMERIZATION VIA ACTIVATION OF THE SMALLG-PROTEIN RAC2

L-selectin mediated adhesion to endothelial cells is a crucial step in the immune response to patho fens (1,2) and in lymphocyte homing (3,4 ). Selectin molecules mediate leukocyte rolling on endothelial cells, the initial step of adhesion (5,6). We have previously shown that stim ulation of Jurkat T-lymphocytes via L-selectin results in activation o f the p21Ras pathway and synthesis of reactive oxygen intermediates (7 ), Here, we show that cellular stimulation via L-selectin induces a ch ange of cytoskeleton organisation demonstrated by a tenfold increase o f actin filament polymerisation. This actin polymerisation is mediated by a Ras and Rac2 regulated pathway, since inhibition of Ras by trans ient transfection of transdominant inhibitory N17Ras or suppression of Rac2 protein expression by antisense oligonucleotides prevents L-sele ctin triggered actin polymerisation. Our results point to a signaling cascade from L-selectin via Ras and Rac2 to actin filaments, which mig ht be important for leukocyte adhesion. (C) 1997 Academic Press.