Complement factors C3a and C5a have distinct hemodynamic effects in the rat

Lavinia M. Proctor, Tyson A. Moore, Peter N. Monk, Sam D. Sanderson, Stephen M. Taylor, Trent M. Woodruff

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

In the rat, C5a infusion mediates well-defined effects including hypotension and neutropenia. Conversely, the comparative effect of C3a in the rat is not yet defined. In the current study, we have investigated C3a receptor (C3aR) activation in the rat, using recombinant human C3a, the C3aR agonist WWGKKYRASKLGLAR, which is a C-terminal analogue of C3a, and a nonpeptide C3aR antagonist SB-290157, as pharmacological tools. In vitro, C3a and WWGKKYRASKLGLAR selectively bound to C3aRs and induced degranulation of C3aR-transfected RBL-2H3 cells. C3a or WWGKKYRASKLGLAR-induced degranulation was dose-dependently antagonized in a surmountable fashion by the nonpeptide C3aR antagonist. Intravenous infusion of C3a and WWGKKYRASKLGLAR to rats induced a rapid, transient and concentration-dependent hypertensive response, which was mediated by C3aR-induced prostanoid release. C3a and WWGKKYRASKLGLAR caused a small drop in circulating neutrophils, but a rise in circulating neutrophils was evident after 90-120 min. In contrast to C3a, C5a infusion resulted in hypotension, and rapid and transient neutropenia. These results demonstrate that C3a and C5a mediate distinct effects on blood pressure and circulating polymorphonuclear leukocytes in the rat.

Original languageEnglish (US)
Pages (from-to)800-806
Number of pages7
JournalInternational Immunopharmacology
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 1 2009

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Keywords

  • Blood pressure
  • C3a
  • C3a agonist
  • C5a
  • Complement
  • Polymorphonuclear leukocytes
  • Rat

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Proctor, L. M., Moore, T. A., Monk, P. N., Sanderson, S. D., Taylor, S. M., & Woodruff, T. M. (2009). Complement factors C3a and C5a have distinct hemodynamic effects in the rat. International Immunopharmacology, 9(6), 800-806. https://doi.org/10.1016/j.intimp.2009.03.002