C-reactive protein induces M-CSF release and macrophage proliferation

J Leukoc Biol. 2009 Feb;85(2):262-7. doi: 10.1189/jlb.0808458. Epub 2008 Nov 13.

Abstract

Inflammation is pivotal in atherosclerosis. M-CSF regulates macrophage growth and differentiation and plays a role in atherogenesis. C-reactive protein (CRP), a cardiovascular risk marker, may promote atherogenesis. However, the effects of CRP on M-CSF release and subsequent macrophage proliferation have not been examined previously. Human aortic endothelial cells (HAEC) were incubated with boiled CRP or native CRP 12.5, 25, and 50 microg/mL for 12-15 h, and M-CSF release was examined by flow cytometry and ELISA. CRP resulted in a significant and dose-dependent increase in M-CSF mRNA and secretion from HAEC as well as human monocyte-derived macrophages (HMDM; P<0.01). Furthermore, conditioned medium (5%) from HAEC pretreated with CRP, when incubated with HMDM, increased macrophage proliferation significantly. This was blocked with M-CSF antibody but not irrelevant antibody. Inhibition of NF-kappaB resulted in significant abrogation of CRP-induced M-CSF release and subsequent macrophage proliferation. Antibodies to CD32 and CD64 but not CD16 abrogated CRP-induced M-CSF release. Thus, CRP up-regulates M-CSF release from HMDM and HAEC and increased macrophage proliferation. These effects appear to be mediated via activation of NF-kappaB via CD32 and CD64. These studies provide further evidence for a proatherogenic role for CRP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • C-Reactive Protein / immunology*
  • Cell Proliferation
  • Culture Media, Conditioned
  • Endothelial Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Macrophage Colony-Stimulating Factor / genetics
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Macrophages / cytology*
  • Macrophages / metabolism*
  • Models, Immunological
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, IgG / metabolism

Substances

  • Culture Media, Conditioned
  • NF-kappa B
  • RNA, Messenger
  • Receptors, IgG
  • Macrophage Colony-Stimulating Factor
  • C-Reactive Protein