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-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 upregulates 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 262-267 |
| Number of pages | 6 |
| Journal | Journal of Leukocyte Biology |
| Volume | 85 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2009 |
Fingerprint
Keywords
- CRP
- Inflammation
- Mechanistic insights
ASJC Scopus subject areas
- Cell Biology
- Immunology
Cite this
C-reactive protein induces M-CSF release and macrophage proliferation. / Devaraj, Sridevi; Yun, Jung Mi; Duncan-Staley, Catherine; Jialal, Ishwarlal.
In: Journal of Leukocyte Biology, Vol. 85, No. 2, 01.02.2009, p. 262-267.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - C-reactive protein induces M-CSF release and macrophage proliferation
AU - Devaraj, Sridevi
AU - Yun, Jung Mi
AU - Duncan-Staley, Catherine
AU - Jialal, Ishwarlal
PY - 2009/2/1
Y1 - 2009/2/1
N2 - 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 upregulates 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.
AB - 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 upregulates 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.
KW - CRP
KW - Inflammation
KW - Mechanistic insights
UR - http://www.scopus.com/inward/record.url?scp=59649100589&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59649100589&partnerID=8YFLogxK
U2 - 10.1189/jlb.0808458
DO - 10.1189/jlb.0808458
M3 - Article
VL - 85
SP - 262
EP - 267
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 2
ER -