PMID- 15802626
OWN - NLM
STAT- MEDLINE
DCOM- 20051221
LR  - 20181201
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 25
IP  - 6
DP  - 2005 Jun
TI  - C-reactive protein-induced in vitro endothelial cell activation is an artefact 
      caused by azide and lipopolysaccharide.
PG  - 1225-30
AB  - 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.
FAU - Taylor, Karolina E
AU  - Taylor KE
AD  - Department of Pharmacology, Therapeutics and Toxicology, Cardiff University, 
      Wales College of Medicine, Cardiff, UK.
FAU - Giddings, John C
AU  - Giddings JC
FAU - van den Berg, Carmen W
AU  - van den Berg CW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050331
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Azides)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (von Willebrand Factor)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
CIN - Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1091-4. PMID: 15923540
CIN - Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):e136. PMID: 16127022
MH  - Artifacts
MH  - Azides/*pharmacology
MH  - C-Reactive Protein/isolation & purification/*pharmacology
MH  - Cell Division/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Dialysis
MH  - Endothelium, Vascular/cytology/*drug effects/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Interleukin-8/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Umbilical Veins/cytology
MH  - von Willebrand Factor/metabolism
EDAT- 2005/04/02 09:00
MHDA- 2005/12/22 09:00
CRDT- 2005/04/02 09:00
PHST- 2005/04/02 09:00 [pubmed]
PHST- 2005/12/22 09:00 [medline]
PHST- 2005/04/02 09:00 [entrez]
AID - 01.ATV.0000164623.41250.28 [pii]
AID - 10.1161/01.ATV.0000164623.41250.28 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1225-30. doi: 
      10.1161/01.ATV.0000164623.41250.28. Epub 2005 Mar 31.