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Oxidized LDL/CD36 interaction induces loss of cell polarity and inhibits macrophage locomotion. Mol Biol Cell 2012 Aug;23(16):3057-68

Date

06/22/2012

Pubmed ID

22718904

Pubmed Central ID

PMC3418302

DOI

10.1091/mbc.E11-12-1051

Scopus ID

2-s2.0-84865209913 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

Cell polarization is essential for migration and the exploratory function of leukocytes. However, the mechanism by which cells maintain polarity or how cells revert to the immobilized state by gaining cellular symmetry is not clear. Previously we showed that interaction between oxidized low-density lipoprotein (oxLDL) and CD36 inhibits macrophage migration; in the current study we tested the hypothesis that oxLDL/CD36-induced inhibition of migration is the result of intracellular signals that regulate cell polarity. Live cell imaging of macrophages showed that oxLDL actuated retraction of macrophage front end lamellipodia and induced loss of cell polarity. Cd36 null and macrophages null for Vav, a guanine nucleotide exchange factor (GEF), did not show this effect. These findings were caused by Rac-mediated inhibition of nonmuscle myosin II, a cell polarity determinant. OxLDL induced dephosphorylation of myosin regulatory light chain (MRLC) by increasing the activity of Rac. Six-thioguanine triphosphate (6-thio-GTP), which inhibits Vav-mediated activation of Rac, abrogated the effect of oxLDL. Activation of the Vav-Rac-myosin II pathway by oxidant stress may induce trapping of macrophages at sites of chronic inflammation such as atherosclerotic plaque.

Author List

Park YM, Drazba JA, Vasanji A, Egelhoff T, Febbraio M, Silverstein RL

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Azepines
CD36 Antigens
COS Cells
Cell Movement
Cell Polarity
Guanosine Triphosphate
HeLa Cells
Humans
Lipoproteins, LDL
Macrophages, Peritoneal
Mice
Mice, Inbred C57BL
Mice, Knockout
Myosin Light Chains
Myosin-Light-Chain Kinase
Naphthalenes
Phosphorylation
Proto-Oncogene Proteins c-vav
Pseudopodia
Thionucleotides
Time-Lapse Imaging
rac GTP-Binding Proteins