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CD36 Modulates Macrophage Spreading and Migration in response to oxidized LDL
Author(s) -
Park Young Mi,
Febbraio Maria,
Silverstein Roy L.
Publication year - 2008
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.22.1_supplement.174.11
Subject(s) - cd36 , scavenger receptor , chemistry , focal adhesion , microbiology and biotechnology , macrophage , phosphorylation , nadph oxidase , proto oncogene tyrosine protein kinase src , cytoskeleton , biochemistry , receptor , biology , oxidative stress , in vitro , cholesterol , cell , lipoprotein
CD36, a class B scavenger receptor expressed on macrophages has been implicated in many biological processes including atherosclerosis. Previous work showed that CD36 mediates uptake of oxidized LDL (oxLDL) and transmits intracellular signals. We hypothesized that oxLDL may affect macrophage adhesion and migration by modulating cytoskeletal function. OxLDL, but not native LDL, inhibited LPS induced efflux of peritoneal macrophages in vivo and MCP‐1 directed macrophage migration in a modified Boyden chamber assay. OxLDL induced rapid spreading on serum‐coated glass, and actin polymerizaton. Western blots of extracts from macrophages incubated with oxLDL showed sustained phosphorylation of focal adhesion kinase (FAK) and dephosphorylation of src homology 2‐containing phosphotyrosine phosphatase, SHP‐2; this was associated with oxidative modification of cysteine residues. These responses were significantly blunted in macrophages from CD36 null mice. OxLDL induced ROS generation in a CD36‐dependent manner, which may provide a mechanism for SHP‐2 modification. Macrophage migration could be restored using antioxidants and NADPH oxidase inhibitors. We conclude that CD36 signaling in response to oxLDL contributes to cytoskeletal rearrangement and modulates macrophage spreading and migration. This may induce trapping of macrophages in the arterial intima and thus promote atherosclerosis.