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- Title
Complement dependency of cardiomyocyte release of mediators during sepsis.
- Authors
Atefi, Gelareh; Zetoune, Firas S.; Herron, Todd J.; Jalife, José; Bosmann, Markus; Al-Aref, Rami; Sarma, J. Vidya; Ward, Peter A.
- Abstract
We have recently shown that antibody-induced blockade of C5a, C5a receptors, or IL-17A greatly reduced the harmful outcomes of sepsis. In the current study, normal cardiomyocytes from young (300 g) male Sprague-Dawley rats responded in vitro to C5a (ED50=55 nM) with release of IL-6 and TNFα, peaking between 2 to 8 h. Neutralizing antibodies to mouse C5a or IL-17A (ED50=40 µg for each, based on improved survival) reduced spontaneous in vitro release of cardiosuppressive cytokines and chemokines in cardiomyocytes obtained from mice with polymicrobial sepsis. A non-neutralizing C5a antibody had no such effects. Cardiomyocytes from septic mice (C57Bl/6) showed increased mRNA for TNFR1, IL-6 (gp80), and C5aR at 6 h after sepsis. Cardiomyocytes from septic C5aR-/- or C5L2-/- mice did not show spontaneous in vitro release of cytokines and chemokines. These data suggest that cardiomyocytes from septic mice release suppressive cytokines in a C5a-, C5aR-, and IL-17A-dependent manner, followed by mediator reactivity with receptors on cardiomyocytes, resulting in defective contractility and relaxation. These data may be relevant to a strategy for the treatment of heart dysfunction developing during sepsis.
- Subjects
HEART cells; SEPSIS; CYTOKINES; INTERLEUKINS; CARDIOMYOPATHIES
- Publication
FASEB Journal, 2011, Vol 25, Issue 7, p2500
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.11-183236