EVIDENCE FOR THE INVOLVEMENT OF PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE3-KINASE IN CD18-MEDIATED ADHESION OF HUMAN NEUTROPHILS TO FIBRINOGEN

The CD18 integrin mediates chemotaxin-induced adhesion of neutrophils to fibrinogen. In neutrophils chemotaxins activate different intracell ular pathways, which metabolize phosphatidylinositol 4,5-bisphosphate. To analyse the functional role of phosphatidylinositol 4,5-bisphospha te 3-kinase in the adhesion response, studies with the fungal metaboli te wortmannin and the chemically unrelated compound LY 294002 were per formed, These compounds inhibited with similar concentration dependenc y chemotaxin-induced formation of [P-32]phosphatidylinositol 3,4,5-tri sphosphate and CD18-mediated adhesion of neutrophils to fibrinogen, bu t did not influence expression of CD18 molecules at the cell surface. These data suggest involvement of phosphatidylinositol 4,5-bisphosphat e S-kinase in chemokine-induced avidity changes of CD18 integrins. (C) 1997 Academic Press.