Journal
EXPERIMENTAL CELL RESEARCH
Volume 290, Issue 1, Pages 120-131Publisher
ELSEVIER INC
DOI: 10.1016/S0014-4827(03)00318-5
Keywords
macrophage; G protein-coupled receptor; PI 3-kinases; chemokines; tyrosine kinase receptors; CSF-1; MCP-1; actin cytoskeleton; cell migration; chemotaxis
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Funding
- Medical Research Council [G0100152, G0100152(56891)] Funding Source: Medline
- MRC [G0100152] Funding Source: UKRI
- Medical Research Council [G0100152] Funding Source: researchfish
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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 PI3Kgamma to macrophage responses to chemoattractants, using bone marrow-derived macrophages from wild-type and PI3Kgamma-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 PI3Kgamma(-/-) mice, although by 30 min MCP-1-induced cell polarization was strongly reduced in PI3Kgamma(-/-) compared to wild-type macrophages. The migration behaviour of the macrophages was analysed by time-lapse microscopy in Dunn chemotaxis chambers. PI3Kgamma(-/-) 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 PI3Kgamma, whereas PI3Kgamma is needed for optimal migration of macrophages to either agonist. (C) 2003 Elsevier Inc. All rights reserved.
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