Derivation of ligands for the complement C3a receptor from the C-terminus of C5a.
Bottom Line: No agonist/antagonist activity was observed at C5a1, but we instead saw that the ligands were able to partially agonize the closely related complement receptor C3a receptor.This was verified in the presence of C3a receptor antagonist SB 290157 and in a stable cell line expressing either C5a1 or C3a receptor alone.C3a agonism has been suggested to be a potential treatment of acute neutrophil-driven traumatic pathologies, and may have great potential as a therapeutic avenue in this arena.
Affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.Show MeSH
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Mentions: Using the xCELLigence, the hits were tested in the presence of both the C3a receptor and C5a1 antagonists, SB 290157 and PMX53, respectively (see Fig. 1C and D). A dose dependent inhibition of the cell index was observed for peptides 20, 31, 47, 49 and 54 in the presence of the competitive antagonist SB 290157 when activated with a concentration of peptide approximating to the EC50. The IC50 of SB 290157 in the presence of peptides 20, 31, 47, 49 and 54 is highlighted in Table 1. No change was observed in the peptide-evoked cell index in the presence of PMX53 (see Fig. 1D). The xCELLigence activation profiles are depicted in Fig. 2, where all the peptides even at a very high dose (100 µM) have a monophasic profile more similar to that of C3a than of C5a. Despite some being partial agonists at the C3a receptor, none of the peptides were able to antagonize C3a activation of HMDM when tested at 10 µM (data not shown).
Affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.