Metabolism and function of 3-D-phosphorylated phosphoinositides in C5a-stimulated eosinophils

Eosinophils play a central role in the pathogenesis of parasitic infections , atopic diseases, and bullous dermatoses. To understand the regulative fun ction of phosphatidylinositol 3-kinases in cell responses of eosinophils, p hospholipid metabolism and production of reactive oxygen metabolites were f ollowed after stimulation with C5a. Measurements of phosphatidylinositol li pids and analysis of deacylated products of separated lipid extracts showed fast and transient formation of phosphatidylinositol 3,4,5-trisphosphate ( PIP3). Cell studies in the presence of the tyrosine kinase blocker genistei n indicated that C5a-stimulated PIP3 formation occurred independently of ty rosine kinase activity. To analyze the function of PI4,5P(2)-3-kinase in eo sinophils, the influence of wortmannin and LY294002 on production of reacti ve oxygen metabolites was studied. Both compounds inhibited with similar co ncentration dependency C5a-induced formation of PIP3 and production of reac tive oxygen metabolites. In summary, these data showed for the first time t he involvement of PI4,5P(2)-3-kinase in the production of reactive oxygen m etabolites in eosinophils. (C) 2000 Academic Press.