Oxidized LDL/CD36 interaction induces loss of cell polarity and inhibits macrophage locomotion.
Oxidized LDL/CD36 interaction induces loss of cell polarity and inhibits macrophage locomotion.
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DOI：
10.1091/mbc.e11-12-1051
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发表时间：
2012-08
影响因子：
3.3
通讯作者：
Silverstein RL
中科院分区：
文献类型：
--
作者：
Park YM;Drazba JA;Vasanji A;Egelhoff T;Febbraio M;Silverstein RL
Oxidized low-density lipoprotein (oxLDL) via CD36 regulates signals for cell polarization and inhibits macrophage migration. The suggested mechanism is nonmuscle myosin II inhibited by Vav/Rac. This indicates that activated Rac induces retraction of cell front and suggests a mechanism of macrophage trapping in atherosclerotic plaque. 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.
