title: High-density lipoproteins neutralize C-reactive protein proinflammatory activity.
abstract: BACKGROUND
  C-reactive protein (CRP), a well-recognized marker of atherosclerosis, has recently been suggested to have a direct proinflammatory effect. The constitutive expression of low levels of CRP in normal plasma suggests the likelihood that a natural factor exists to neutralize the effect of CRP. This factor(s) has not yet been identified. Method and Results- The proinflammatory effect of CRP was measured by the induction of inflammatory adhesion molecules in human umbilical vein endothelial cells (HUVECs). We show that CRP significantly induced upregulation of adhesion molecules in both protein and mRNA levels. The CRP-induced expression of these inflammatory adhesion molecules was completely suppressed when the cells were preincubated with a physiological concentration (1 mg/mL apolipoprotein A-I) of HDLs derived from human plasma (native HDL) or reconstituted HDL (rHDL) at a very low concentration (0.01 mg/mL apolipoprotein A-I). A novel mechanism of HDL inhibition is likely to operate, because (1) rHDL was 100 times more potent than native HDL, (2) preincubation with HDL and its sustained presence were obligatory, and (3) oxidized 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine was the fundamental active component.
  
  
  CONCLUSIONS
  The CRP-induced upregulation of inflammatory adhesion molecules in HUVECs was completely prevented by HDL via their oxidized phospholipid components.
authors.affiliation: Division of Human Immunology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Wadham
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Albanese
authors.forename: Jane
authors.initials: J
authors.lastname: Roberts
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bagley
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Gamble
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Mathew A
authors.initials: MA
authors.lastname: Vadas
authors.forename: Pu
authors.initials: P
authors.lastname: Xia
mesh_terms: D000818:Animals; D001011:Aorta; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002417:Cattle; D002448:Cell Adhesion; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008081:Liposomes / Q000494:pharmacology; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D020298:U937 Cells / Q000187:drug effects; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; D019040:E-Selectin; D008075:Lipoproteins, HDL; D008081:Liposomes; D010713:Phosphatidylcholines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C055402:1-palmitoyl-2-linoleoylphosphatidylcholine; D002097:C-Reactive Protein