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C‐reactive protein induces M‐CSF release and macrophage proliferation
Author(s) -
Devaraj Sridevi,
Yun JungMi,
DuncanStaley Catherine,
Jialal Ishwarlal
Publication year - 2009
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0808458
Subject(s) - cd64 , macrophage , flow cytometry , inflammation , antibody , cd16 , immunology , secretion , c reactive protein , tumor necrosis factor alpha , monocyte , biology , endocrinology , chemistry , medicine , microbiology and biotechnology , in vitro , biochemistry , immune system , cd3 , cd8
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‐κB 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‐κB via CD32 and CD64. These studies provide further evidence for a proatherogenic role for CRP.