Sridevi Devaraj1, Ishwarlal Jialal. 1. Laboratory for Atherosclerosis and Metabolic Research, University of California, Davis, Medical Center, Sacramento, CA 95817, USA.
Abstract
OBJECTIVE: Inflammation is pivotal in atherosclerosis. Monocyte-macrophages are crucial in atherosclerosis. Monocytes can develop into subsets: classically (M1) or alternatively (M2) activated cells. Several studies point to a proinflammatory role for C-reactive protein (CRP). Because there is a paucity of data on the effects of CRP on macrophage phenotype, we tested effects of CRP on macrophage polarization. METHODS AND RESULTS: Monocytes were incubated with CRP (0 to 50 μg/mL) and differentiated into macrophages for 7 days. Phenotypic characterization of M1 and M2 macrophages was performed using flow cytometry. CRP treatment resulted in increased population of M1 macrophages (tumor necrosis factor [TNF]/interleukin [IL]-12/C-C chemokine receptor 2, TNF/IL-12/monocyte chemotactic protein-1, or TNF/IL-1/IL-12). These effects were not abrogated by polymixin B or small interfering RNA to Toll-like receptor-4, but they were abrogated by boiled CRP. Administration of human CRP to rats in vivo increased polarization of macrophages to M1 phenotype compared with human serum albumin. When macrophages were primed to the M2 phenotype with IL-4, addition of CRP resulted in significantly increased secretion of TNF-α, MCP-1, and IL-1 and conversion of macrophages from the M2 to the M1 phenotype. CRP failed to prime macrophages to the M1 phenotype in presence of CD32/CD64 small interfering RNA or dominant-negative nuclear factor kappa B. CONCLUSION: Collectively, these results further support a role for CRP in promoting differentiation of human monocytes toward a proinflammatory M1 phenotype.
OBJECTIVE:Inflammation is pivotal in atherosclerosis. Monocyte-macrophages are crucial in atherosclerosis. Monocytes can develop into subsets: classically (M1) or alternatively (M2) activated cells. Several studies point to a proinflammatory role for C-reactive protein (CRP). Because there is a paucity of data on the effects of CRP on macrophage phenotype, we tested effects of CRP on macrophage polarization. METHODS AND RESULTS: Monocytes were incubated with CRP (0 to 50 μg/mL) and differentiated into macrophages for 7 days. Phenotypic characterization of M1 and M2 macrophages was performed using flow cytometry. CRP treatment resulted in increased population of M1 macrophages (tumor necrosis factor [TNF]/interleukin [IL]-12/C-C chemokine receptor 2, TNF/IL-12/monocyte chemotactic protein-1, or TNF/IL-1/IL-12). These effects were not abrogated by polymixin B or small interfering RNA to Toll-like receptor-4, but they were abrogated by boiled CRP. Administration of humanCRP to rats in vivo increased polarization of macrophages to M1 phenotype compared with humanserum albumin. When macrophages were primed to the M2 phenotype with IL-4, addition of CRP resulted in significantly increased secretion of TNF-α, MCP-1, and IL-1 and conversion of macrophages from the M2 to the M1 phenotype. CRP failed to prime macrophages to the M1 phenotype in presence of CD32/CD64 small interfering RNA or dominant-negative nuclear factor kappa B. CONCLUSION: Collectively, these results further support a role for CRP in promoting differentiation of human monocytes toward a proinflammatory M1 phenotype.
Authors: Fina Lovren; Yi Pan; Adrian Quan; Paul E Szmitko; Krishna K Singh; Praphulla C Shukla; Milan Gupta; Lawrence Chan; Mohammed Al-Omran; Hwee Teoh; Subodh Verma Journal: Am J Physiol Heart Circ Physiol Date: 2010-07-09 Impact factor: 4.733
Authors: Mark B Pepys; Gideon M Hirschfield; Glenys A Tennent; J Ruth Gallimore; Melvyn C Kahan; Vittorio Bellotti; Philip N Hawkins; Rebecca M Myers; Martin D Smith; Alessandra Polara; Alexander J A Cobb; Steven V Ley; J Andrew Aquilina; Carol V Robinson; Isam Sharif; Gillian A Gray; Caroline A Sabin; Michelle C Jenvey; Simon E Kolstoe; Darren Thompson; Stephen P Wood Journal: Nature Date: 2006-04-27 Impact factor: 49.962
Authors: Amit Saxena; Peter M Izmirly; Sung Won Han; Paraskevi Briassouli; Tania L Rivera; Hua Zhong; Deborah M Friedman; Robert M Clancy; Jill P Buyon Journal: J Am Coll Cardiol Date: 2015-08-25 Impact factor: 24.094