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

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64 Scopus citations

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.-Speidl, W. S., Kastl, S. P., Hutter, R., Katsaros, K. M., Kaun, C., Bauriedel, G., Maurer, G., Huber, K., Badimon, J. J., Wojta, J. 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.

Original languageEnglish
Pages (from-to)35-44
Number of pages10
JournalFASEB Journal
Volume25
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Keywords

  • Atherosclerosis
  • Matrix metalloproteinase
  • Plaque rupture

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