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Requirement for PI 3-kinase γ in macrophage migration to MCP-1 and CSF-1

Jones, Gareth E., Prigmore, Elena, Calvez, Ronan, Hogan, Catherine, Dunn, Graham A., Hirsch, Emilio, Wymann, Matthias P. and Ridley, Anne J. 2003. Requirement for PI 3-kinase γ in macrophage migration to MCP-1 and CSF-1. Experimental Cell Research 290 (1) , pp. 120-131. 10.1016/S0014-4827(03)00318-5

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Abstract

Phosphoinositide 3-kinases (PI3Ks) are important regulators of cell migration. The PI3K isoform γ is primarily expressed in haematopoietic cells, and is activated by G protein-coupled receptors (GPCRs). Here, we investigate the contribution of PI3Kγ to macrophage responses to chemoattractants, using bone marrow-derived macrophages from wild-type and PI3Kγ-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 PI3Kγ−/− mice, although by 30 min MCP-1-induced cell polarization was strongly reduced in PI3Kγ−/− compared to wild-type macrophages. The migration behaviour of the macrophages was analysed by time-lapse microscopy in Dunn chemotaxis chambers. PI3Kγ−/− macrophages showed reduced migration speed and translocation, and no chemotaxis to MCP-1. Interestingly, there was also a reduction in migration efficiency in PI3Kγ−/− 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 PI3Kγ, whereas PI3Kγ is needed for optimal migration of macrophages to either agonist.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Publisher: Elsevier
ISSN: 0014-4827
Last Modified: 04 Jun 2017 06:39
URI: http://orca-mwe.cf.ac.uk/id/eprint/63372

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