The phosphatidylinositol 3-kinase inhibitor wortmannin markedly reduces chemotactic peptide-induced locomotion and increases in cytoskeletal actin in human neutrophils

Localization of p21-activated kinase 1 (PAK1) to pseudopodia, membrane ruffles, and phagocytic cups in activated human neutrophils

“…These results suggest that additional mechanisms are likely to be operative in regulating actin cytoskeletal changes during the phagocytic response. Previous studies have shown that wortmannin specifically inhibited F-actin organization rather than actin polymerization [34]. The data obtained herein, where PAK1 did not translocate to the cytoskeleton in the presence of cytochalasin D or wortmannin, suggest that PAK1 may be Fig.…”

“…Redistribution of PAK1 to the cytoskeleton in response to cell surface receptor activation is inhibited by wortmannin and cytochalasin D Wortmannin and cytochalasin D have both been reported to modulate the functional responses of leukocytes through effects on the actin cytoskeleton [12,[34][35][36]. We observed that 10 µM cytochalasin D, a potent inhibitor of actin polymerization, added to neutrophils 10 min before stimulation with fMLP blocked cell polarization and the incorporation of F-actin into cell surface extensions.…”

“…The PI 3-kinase inhibitor wortmannin blocks chemotactic peptide-induced development of cell polarity, increases in cytoskeletal actin, and phagocytosis in human neutrophils [8,10,12,[34][35][36][37][38]41]. We examined the effect of nanomolar (i.e., PI 3-kinase-specific) concentrations of wortmannin on PAK1 localization.…”

Neutrophils: Molecules, Functions and Pathophysiological Aspects

“…The role of PI3-Kinase in neutrophil adhesion promoted by G-protein-coupled receptors is not clearly defined (Akasaki et al, 1999;Shimizu and Huntiii, 1996). Specific PI3-Kinase inhibitors block chemoattractant-induced neutrophil locomotion or homotypic aggregation, but have no effect on integrin CD11b/CD18 expression and activation triggered by these agonists (Capodici et al, 1998;Jones et al, 1998;Niggli and Keller, 1997).…”

Vav1: A Key Player in Agonist-Induced Differentiation of Promyelocytes from Acute Myeloid Leukemia (APL)

“…The response to ATRA and the downstream effects of PI3K observed during the induced differentiation support the notion that PI3K is recruited in the path controling cytoskeleton in mature granulocytes. In fact, PI3K is activated in response to chemotactic factors in murine and human neutrophils (Cicchetti et al, 2002;Niggli & Keller, 1997;Stephens et al, 2002) in which newly produced PIP 3 is involved in determining the localization and possibly the crosslinking/stabilization of actin filaments (Chen et al, 2003;Hannigan et al, 2002;Wang et al, 2002). In vitro experiments have demonstrated that PI3K may affect actin-related modifications of cytoskeleton also by directly affecting PAK kinase activity (Menard & Mattingly, 2004).…”