C-reactive protein upregulates complement-inhibitory factors in endothelial cells

Circulation. 2004 Feb 24;109(7):833-6. doi: 10.1161/01.CIR.0000117087.27524.0E. Epub 2004 Feb 16.

Abstract

Background: Because complement-mediated vascular injury participates in atherosclerosis and C-reactive protein (CRP) can activate the complement cascade, we sought to determine whether CRP affects the expression of the protective complement-inhibitory factors on the cell surface of endothelial cells (ECs).

Methods and results: Human coronary artery or human saphenous vein ECs were incubated with CRP (0 to 100 microg/mL, 0 to 72 hours), and the expression of the complement-inhibitory proteins decay-accelerating factor (DAF), membrane cofactor protein (CD46), and CD59 were measured by flow cytometry. Incubation with CRP resulted in a significant increase in the expression of all 3 proteins. CRP-induced upregulation of DAF required increased steady-state mRNA and de novo protein synthesis. The increased expression of complement-inhibitory proteins was functionally effective, resulting in significant reduction of complement-mediated lysis of antibody-coated human saphenous vein ECs.

Conclusions: These observations provide evidence for a possible protective role for CRP in atherogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics
  • Arteriosclerosis / metabolism
  • Arteriosclerosis / prevention & control*
  • C-Reactive Protein / pharmacology
  • C-Reactive Protein / physiology*
  • CD55 Antigens / biosynthesis*
  • CD55 Antigens / genetics
  • CD59 Antigens / biosynthesis*
  • CD59 Antigens / genetics
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Coronary Vessels / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Gene Expression Regulation / drug effects
  • Humans
  • Membrane Cofactor Protein
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • RNA, Messenger / biosynthesis
  • Saphenous Vein / cytology

Substances

  • Antigens, CD
  • CD46 protein, human
  • CD55 Antigens
  • CD59 Antigens
  • Membrane Cofactor Protein
  • Membrane Glycoproteins
  • RNA, Messenger
  • C-Reactive Protein