A ROLE FOR THE ACTIN-BUNDLING PROTEIN L-PLASTIN IN THE REGULATION OF LEUKOCYTE INTEGRIN FUNCTION

Regulation of leukocyte integrin avidity is a crucial aspect of inflam mation and immunity. The actin cytoskeleton has an important role in t he regulation of integrin function, but the cytoskeletal proteins invo lved are largely unknown. Because inflammatory stimuli that activate i ntegrin-mediated adhesion in human polymorphonuclear neutrophils (PMN) and monocytes cause phosphorylation of the actin-bundling protein L-p lastin, we tested whether L-plastin phosphorylation was involved in in tegrin activation, L-plastin-derived peptides that included the phosph orylation site (Ser-5) rapidly induced leukocyte integrin-mediated adh esion when introduced into the cytosol of freshly isolated primary hum an PMN and monocytes. Substitution of Ala for Ser-5 abolished the abil ity of the peptide to induce adhesion. Peptide-induced adhesion was se nsitive to pharmacologic inhibition of phosphoinositol 3-kinase and pr otein kinase C, but adhesion induced by a peptide containing a phospho serine at position 5 was insensitive to inhibition. These data establi sh a novel role for L-plastin in the regulation of leukocyte adhesion and suggest that many signaling events implicated in integrin regulati on act via induction of L-plastin phosphorylation.