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

Walter S Speidl; Stefan P Kastl; Randolph Hutter; Katharina M Katsaros; Christoph Kaun; Gerhard Bauriedel; Gerald Maurer; Kurt Huber; Juan J Badimon; Johann Wojta

doi:10.1096/fj.10-156083

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.

Authors

Walter S Speidl¹, Stefan P Kastl, Randolph Hutter, Katharina M Katsaros, Christoph Kaun, Gerhard Bauriedel, Gerald Maurer, Kurt Huber, Juan J Badimon, Johann Wojta

Affiliation

¹ Department of Internal Medicine II, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

PMID: 20813982
DOI: 10.1096/fj.10-156083

Abstract

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

Substances

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