P1 3-kinase-dependent and independent chemotaxis of human neutrophil leukocytes

The migration of neutrophil leukocytes to inflammatory sites is important for the elimination of microorganisms but can under pathological conditions lead to severe tissue damage. The initial chemotactic response is elicited by classical chemoattractants, such as fMet-Leu-Phe or the chemokine interleukin-8 which ligate to G-protein coupled receptors. Neutrophils show also a delayed chemotactic response to growth factors, such as platelet derived growth factor (PDGF) or tumor growth factor (TGF beta). We describe here that classical chemoattractants and growth factors stimulate neutrophil chemotaxis through different signal transduction pathways. Wortmannin, a selective phosphatidylinositol 3-kinase inhibitor, completely blocks growth factor stimulated chemotaxis while having no effect on neutrophil migration stimulated with classical chemoattractants. The results suggest that eel migration can be selectively controlled through the inhibition of distinct signal transduction events. (C) 1995 Academic Press. Inc.