Evidence for the involvement of phosphatidylinositol 4,5-bisphosphate 3-kinase in CD18-mediated adhesion of human neutrophils to fibrinogen

Abstract

The CD18 integrin mediates chemotaxin-induced adhesion of neutrophils to fibrinogen. In neutrophils chemotaxins activate different intracellular pathways, which metabolize phosphatidylinositol 4,5-bisphosphate. To analyse the functional role of phosphatidylinositol 4,5-bisphosphate 3-kinase in the adhesion response, studies with the fungal metabolite wortmannin and the chemically unrelated compound LY 294002 were performed. These compounds inhibited with similar concentration dependency chemotaxin-induced formation of [32P]phosphatidylinositol 3,4,5-trisphosphate and CD18-mediated adhesion of neutrophils to fibrinogen, but did not influence expression of CD18 molecules at the cell surface. These data suggest involvement of phosphatidylinositol 4,5-bisphosphate 3-kinase in chemokine-induced avidity changes of CD18 integrins.