C-reactive protein induces M-CSF release and macrophage proliferation.
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.
Devaraj
Sridevi
S
Laboratory for Atherosclerosis and Metabolic Research, Department of Medical Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA.
Yun
Jung-Mi
JM
Duncan-Staley
Catherine
C
Jialal
Ishwarlal
I
D002097:C-Reactive Protein / Q000276:immunology*; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D018448:Models, Immunological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism
D017077:Culture Media, Conditioned; D016328:NF-kappa B; D012333:RNA, Messenger; D017452:Receptors, IgG; D016173:Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein