Journal of Leukocyte Biology
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Published online before print November 13, 2008
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0808458

Received for publication August 1, 2008.
Revised October 22, 2008.
Accepted for publication October 29, 2008.

Article

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

Sridevi Devaraj , Jung-Mi Yun , Catherine Duncan-Staley , and Ishwarlal Jialal @

Laboratory for Atherosclerosis and Metabolic Research, Department of Medical Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, California, USA

@ To whom correspondence should be addressed. E-mail: ishwarlal.jialal{at}ucdmc.ucdavis.edu.


  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 µg/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-{kappa}B 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-{kappa}B via CD32 and CD64. These studies provide further evidence for a proatherogenic role for CRP.

Key Words: mechanistic insights • CRP






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