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A membrane‐permeant ester of phosphatidylinositol 3,4,5‐trisphosphate (PIP 3 ) is an activator of human neutrophil migration
Author(s) -
Niggli Verena
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01534-9
Subject(s) - phosphatidylinositol , chemotaxis , pi , activator (genetics) , chemistry , kinase , motility , microbiology and biotechnology , biophysics , biochemistry , receptor , biology
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 (PIP 3 ), on neutrophil migration. To this end, a membrane‐permeant ester of PIP 3 , dilauroyl phosphatidylinositol 3,4,5‐trisphosphate‐heptakis‐(acetooxymethyl)ester (PIP 3 /AM) was used. PIP 3 /AM (ED 50 : 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 PIP 3 /AM‐induced motility.