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CD36 Mediates Macrophage Spreading and Migration in response to oxidized LDL.
Author(s) -
Park Young Mi,
Febbraio Maria,
Silverstein Roy L.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a634-b
Subject(s) - cd36 , microbiology and biotechnology , colocalization , macrophage , foam cell , chemistry , scavenger receptor , actin cytoskeleton , cytoskeleton , phalloidin , actin , biology , receptor , in vitro , biochemistry , cell , lipoprotein , cholesterol
CD36, a transmembrane glycoprotein receptor expressed on monocytes/macrophages has been implicated in multiple biological processes including atherosclerosis. Previous work established that macrophage CD36 binds and mediates uptake of oxidized LDL (oxLDL) and transmits intracellular signals through src and MAP kinases. We hypothesized that oxLDL may affect cellular adhesion and migration by modulating cytoskeletal function. We found that OxLDL, but not native LDL inhibited MCP‐1 induced mouse macrophage migration in a modified Boyden chamber assay. Macrophages isolated from CD36 null mice were not inhibited. Similarly, OxLDL but not native LDL induced rapid macrophage spreading on tissue culture plastic. OxLDL‐induced spreading was delayed in CD36 null macrophages. Western blots of protein extracts from mouse resident peritoneal macrophages immunoprecipitated with anti‐CD36 IgA showed that actin co‐precipitated with CD36. Flow cytometry of macrophages incubated with fluorescently labeled phalloidin showed that polymerized actin formation was induced by oxLDL. This response was significantly blunted in macrophages from CD36 null mice. We conclude that CD36 associates physically with actin and may regulate actin polymerization in response to oxLDL, facilitating cell spreading and inhibiting MCP‐1 induced migration. These observations together suggest that CD36 signaling in response to OxLDL may contribute to cytoskeletal rearrangements necessary for oxLDL internalization and to trapping of macrophages in the vessel wall, and thus promote atherosclerotic lesion development. (Supported by NHLBI RO1 HL70083 and P01 HL46403)