The complement component C5a is present in human coronary lesions in vivo and induces the expression of MMP-1 and MMP-9 in human macrophages in vitro

FASEB J. 2011 Jan;25(1):35-44. doi: 10.1096/fj.10-156083. Epub 2010 Sep 2.


The complement component C5a is formed during activation of the complement cascade and exerts chemotactic and proinflammatory effects. Macrophages, which are localized in the rupture-prone shoulder regions of coronary plaques, are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). When human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased. Furthermore, C5a up-regulated MMP-1 and MMP-9 antigens and activity, as determined by ELISA and specific activity assays. These effects were blocked by antibodies against the receptor C5aR/CD88. In addition, blocking experiments revealed that MMP-1 expression was mediated by activation of the transcription factor AP-1, and MMP-9 expression was induced by activation of NF-κB and AP-1. Immunohistochemical analysis of human coronary plaques demonstrated the colocalization of C5a, MMP-1, and MMP-9 in vivo. Together, these observations indicate that activation of the complement cascade and formation of C5a may play a role in the onset of acute coronary events by induction of MMPs in atherosclerotic lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Complement C5a / genetics
  • Complement C5a / metabolism*
  • Complement C5a / pharmacology
  • Coronary Vessels / metabolism*
  • Coronary Vessels / pathology
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Humans
  • Immunohistochemistry
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Masoprocol / pharmacology
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Plaque, Atherosclerotic / metabolism*
  • Plaque, Atherosclerotic / pathology
  • Quinazolines / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Anaphylatoxin C5a / metabolism
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor AP-1 / antagonists & inhibitors
  • Transcription Factor AP-1 / metabolism


  • 6-amino-4-(4-n-pentyloxy)phenethylaminoquinazoline
  • NF-kappa B
  • Quinazolines
  • RNA, Messenger
  • Receptor, Anaphylatoxin C5a
  • Recombinant Proteins
  • Transcription Factor AP-1
  • Masoprocol
  • Complement C5a
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1