CRP enhances soluble LOX-1 release from macrophages by activating TNF-α converting enzyme

Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) play an important role in the development and progression of atherosclerosis. We hypothesized that the inflammatory marker C-reactive protein (CRP) might stimulate sLOX-1 release by activating tumor necrosis factor-alpha converting enzyme (TACE). Macrophages differentiated from THP-1 cells were stimulated with TNF-alpha and further treated with CRP in the absence or presence of specific inhibitors or small interfering RNA (siRNA). Our results showed that CRP increased sLOX-1 release from activated macrophages in a dose-dependent manner and that these effects were regulated by Fc gamma receptor II (Fc gamma RII)-mediated p47(phox) phosphorylation, reactive oxygen species (ROS) production, and TACE activation. CRP also enhanced sLOX-1 release from macrophages derived from peripheral blood mononuclear cells (PBMC) of patients with acute coronary syndrome (ACS). Pretreatment with antibody against Fc gamma RII or with CD32 siRNA, p47(phox) siRNA, apocynin, N-acetylcysteine, tumor necrosis factor-alpha protease inhibitor 1 (TAPI-1) or TACE siRNA attenuated sLOX-1 release induced by CRP. CRP also elevated serum sLOX-1 levels in a rabbit model of atherosclerosis.jlr Thus, CRP might stimulate sLOX-1 release, and the underlying mechanisms possibly involved Fc gamma RII-mediated p47(phox) phosphorylation, ROS production, and TACE activation.-Zhao, X. Q., M. W. Zhang, F. Wang, Y. X. Zhao, J. J. Li, X. P. Wang, P. L. Bu, J. M. Yang, X. L. Liu, M. X. Zhang, F. Gao, C. Zhang, and Y. Zhang. CRP enhances soluble LOX-1 release from macrophages by activating TNF-alpha converting enzyme. J. Lipid Res. 52: 923-933.