C-reactive protein polarizes human macrophages to an M1 Phenotype and inhibits transformation to the M2 phenotype

Sridevi Devaraj, Ishwarlal Jialal

Research output: Contribution to journalArticle

78 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1397-1402
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • cytokines
  • macrophages
  • vascular biology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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