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C-reactive protein-induced in vitro endothelial cell activation is an artefact caused by azide and lipopolysaccharide
被引:135
作者:
Taylor, KE
Giddings, JC
van den Berg, CW
机构:
[1] Cardiff Univ, Wales Coll Med, Wales Heart Res Inst, Dept Pharmacol Therapeut & Toxicol, Cardiff CF14 4XN, S Glam, Wales
[2] Cardiff Univ, Wales Coll Med, Dept Haematol, Cardiff CF14 4XN, S Glam, Wales
关键词:
C-reactive protein;
endothelial cells;
azide;
LPS;
D O I:
10.1161/01.ATV.0000164623.41250.28
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Objective - C- reactive protein ( CRP) has been proposed to be an independent risk factor for cardiovascular disease. In vitro studies investigating the mechanism behind this have used purified commercial CRP ( cCRP) and endothelial cells. We investigated the role of contaminants in cCRP preparations. Methods and Results - Human umbilical vein endothelial cells and the human endothelial cell line EA. hy926 were incubated with Escherichia coli - derived cCRP, in- house - generated azide- free recombinant, and ascites- purified CRP, azide, or lipopolysaccharide ( LPS) equivalent to the concentration present in cCRP preparations. Cells were investigated for change in cell proliferation, morphology, apoptosis, and expression of endothelial NO synthase and intercellular adhesion molecule- 1. Cell supernatants were assessed for monocyte chemoattractant protein- 1 ( MCP- 1), interleukin- 8, von Willebrand factor secretion, and pH change. Only cCRP was able to induce all activation events analyzed; however, this ability was lost on extensive dialysis, suggesting that low molecular weight contaminants were responsible for these events. Indeed, the effects of cCRP were mirrored by azide or LPS. Conclusions - We investigated a wide range of effects on endothelial cells ascribed to CRP; however, azide and LPS, but never CRP itself, were responsible for the cell activation events. We conclude that CRP, per se, does not activate endothelial cells.
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页码:1225 / 1230
页数:6
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