A membrane‐permeant ester of phosphatidylinositol 3,4,5‐trisphosphate (PIP3) is an activator of human neutrophil migration

[摘要]

Activity of phosphatidylinositol (PI) 3-kinase is required for optimal migration of human neutrophils [Niggli and Keller (1999) Eur. J. Pharmacol. 335, 43–52]. We have tested the direct effect of a product of PI 3-kinase, phosphatidylinositol 3,4,5-trisphosphate (PIP₃), on neutrophil migration. To this end, a membrane-permeant ester of PIP₃, dilauroyl phosphatidylinositol 3,4,5-trisphosphate-heptakis-(acetooxymethyl)ester (PIP₃/AM) was used. PIP₃/AM (ED₅₀: 10–17 μM) induced development of polarity and accumulation of F-actin in the leading lamellae in up to 70% of the cells. These cells exhibited stimulated random migration, comparable to that observed in uniform concentrations of chemotactic peptide. Evidence is provided for a role of Rho-kinase and for activation of PI 3-kinase in a positive feedback loop in PIP₃/AM-induced motility.

[学科分类] 生物化学/生物物理

[关键词] Neutrophil;Cell migration;Phosphatidylinositol 3;4;5-trisphosphate;Rho-activated kinase;Phosphatidylinositol 3-kinase;fNLPNTL;N-formyl-L-norleucyl-L-leucyl-L-phenylalanyl-L-norleucyl-L-tyrosyl-L-lysine;ERK;extracellular signal-regulated kinase;HSA;human serum albumin;MAPK;mitogen-activated protein kinase;PI 3-kinase;phosphatidylinositol 3-kinase;PI(3;4)P2;phosphatidylinositol 3;4-diphosphate;PIP3;phosphatidylinositol 3;4;5-trisphosphate;PIP3/AM;dilauroyl phosphatidylinositol 3;4;5-trisphosphate-heptakis-(acetooxymethyl)ester