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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
Author(s) -
Speidl Walter S.,
Kasd Stefan P.,
Hutter Randolph,
Katsaros Katharina M.,
Kaun Christoph,
Bauriedel Gerhard,
Maurer Gerald,
Huber Kurt,
Badimon Juan J.,
Wojta Johann
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-156083
Subject(s) - matrix metalloproteinase , c5a receptor , in vivo , complement system , in vitro , microbiology and biotechnology , chemistry , proinflammatory cytokine , inflammation , receptor , biology , immunology , immune system , biochemistry
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. FASEB J. 25, 35–44 (2011). www.fasebj.org