Species dependence for binding of small molecule agonist and antagonists to the C5a receptor on polymorphonuclear leukocytes

Trent M. Woodruff, Anna J. Strachan, Sam D. Sanderson, Peter N. Monk, Allan K. Wong, David P. Fairlie, Stephen M. Taylor

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

This study investigated the receptor binding affinities of a C5a agonist and cyclic antagonists for polymorphonuclear leukocytes (PMNs) isolated from human, sheep, pig, dog, rabbit, guinea pig, rat and mouse. The affinities of the two small molecule antagonists, F-[OPdChaWR] and AcF-[OPdChaWR], and the agonist, YSFKPMPLaR, revealed large differences in C5a receptor (C5aR) affinities between species. The antagonists bound to human, rat and dog PMNs with similar high affinities, but with lower affinities to PMNs from all other species. The C5a agonist also bound with varying affinities between species, but showed a different affinity profile to the antagonists. In contrast, recombinant human C5a had similar affinity for PMNs of all species investigated. The low correlation between the affinities of the antagonists and the agonist between species either suggests that different receptor residues are important for distinguishing between agonist/antagonist binding, or that the agonist and antagonist peptides bind to two distinct sites within the C5aR.

Original languageEnglish (US)
Pages (from-to)171-177
Number of pages7
JournalInflammation
Volume25
Issue number3
DOIs
StatePublished - 2001

Keywords

  • C5a agonist
  • C5a antagonist
  • Leukocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Woodruff, T. M., Strachan, A. J., Sanderson, S. D., Monk, P. N., Wong, A. K., Fairlie, D. P., & Taylor, S. M. (2001). Species dependence for binding of small molecule agonist and antagonists to the C5a receptor on polymorphonuclear leukocytes. Inflammation, 25(3), 171-177. https://doi.org/10.1023/A:1011036414353