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Originally published online as doi:10.1189/jlb.0808458 on November 13, 2008

Published online before print November 13, 2008
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(Journal of Leukocyte Biology. 2009;85:262-267.)
© 2009 Society for Leukocyte Biology

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

Sridevi Devaraj, Jung-Mi Yun, Catherine Duncan-Staley and Ishwarlal Jialal1

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

1 Correspondence: Laboratory for Atherosclerosis and Metabolic Research, Department of Medical Pathology and Laboratory Medicine, UC Davis Medical Center, 4635 2nd Avenue, Room #3000, Research Building 1, Sacramento, CA 95817, USA. 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 • inflammation