Role of granulocytes and C5a in myocardial response to zymosan-activated serum

G. L. Stahl, M. P. Fletcher, Ezra A Amsterdam, J. C. Longhurst

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Abstract

Although previous studies have demonstrated that complement (C)5a causes myocardial ischemia and mechanical dysfunction, the cardiac response of endogenously produced C5a and C5a des-Arg in zymosan-activated serum (ZAS) and the critical role of granulocytes in this process are poorly understood. Therefore, we compared the coronary and cardiac effects of ZAS and purified C5a and investigated the role of leukocyte adhesion-promoting receptors (i.e., CD11/CD18). Like purified C5a, ZAS (0.5 ml) significantly reduced coronary artery blood flow and regional segment shortening, whereas coronary venous granulocyte concentration and myocardial lactate extraction were significantly decreased. A monoclonal antibody (MoAb) to C5a/C5a des-Arg attenuated ZAS-induced cardiac alterations. Three minutes of continuous infusion of C5a or ZAS induced sustained decreases in coronary venous granulocyte concentrations, although coronary flow and segment shortening returned to control levels after 2 min. Another MoAb, IB4, directed against CD18, significantly inhibited ZAS-induced granulocyte extraction and associated cardiac effects. Thus, cardiac dysfunction occurs after activation of the complement cascade with zymosan resulting in extraction of granulocytes mediated by the CD18 adherence glycoprotein. Furthermore, intramyocardial retention of granulocytes appears necessary for the initial and full ZAS-induced cardiac dysfunction.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume261
Issue number1 30-1
StatePublished - 1991

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Keywords

  • Adherence
  • Complement
  • Coronary blood flow
  • Ischemia
  • Leukocyte adhesion-promoting receptors
  • Monoclonal antibody IB4
  • Segment shortening

ASJC Scopus subject areas

  • Physiology

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