Requirement for PI 3-kinase [gamma] in macrophage migration to MCP-1 and CSF-1[white star].
Jones, Gareth E. a,1; Prigmore, Elena b,1; Calvez, Ronan c; Hogan, Catherine a; Dunn, Graham A. a; Hirsch, Emilio d; Wymann, Matthias P. c; Ridley, Anne J. b,e,*
[Article] Experimental Cell Research. 290(1):120-131, October 2003.

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Phosphoinositide 3-kinases (PI3Ks) are important regulators of cell migration. The PI3K isoform [gamma] is primarily expressed in haematopoietic cells, and is activated by G protein-coupled receptors (GPCRs). Here, we investigate the contribution of PI3K[gamma] to macrophage responses to chemoattractants, using bone marrow-derived macrophages from wild-type and PI3K[gamma]-null mice. We observe that early membrane ruffling induced by MCP-1, which activates a GPCR, or by CSF-1, which activates a tyrosine kinase receptor, is unaltered in PI3K[gamma]-/- mice, although by 30 min MCP-1-induced cell polarization was strongly reduced in PI3K[gamma]-/- compared to wild-type macrophages. The migration behaviour of the macrophages was analysed by time-lapse microscopy in Dunn chemotaxis chambers. PI3K[gamma]-/- macrophages showed reduced migration speed and translocation, and no chemotaxis to MCP-1. Interestingly, there was also a reduction in migration efficiency in PI3K[gamma]-/- macrophages stimulated with CSF-1 although early CSF-1R signalling was normal. These results indicate that the initial actin reorganization induced by either a GPCR or tyrosine kinase receptor agonist is not dependent on PI3K[gamma], whereas PI3K[gamma] is needed for optimal migration of macrophages to either agonist.

(C) 2003Elsevier, Inc.