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Derivation of ligands for the complement C3a receptor from the C-terminus of C5a.

Halai R, Bellows-Peterson ML, Branchett W, Smadbeck J, Kieslich CA, Croker DE, Cooper MA, Morikis D, Woodruff TM, Floudas CA, Monk PN - Eur. J. Pharmacol. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.

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xCELLigence response profiles for C3a and C5a at 100 nM, and peptides 20, 31, 47, 49 and 54 at 100 μM. A two-peak profile is evident for C5a, whereas a single peak profile is apparent for C3a. Peptide profiles more closely resemble C3a activation than C5a activation.
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f0010: xCELLigence response profiles for C3a and C5a at 100 nM, and peptides 20, 31, 47, 49 and 54 at 100 μM. A two-peak profile is evident for C5a, whereas a single peak profile is apparent for C3a. Peptide profiles more closely resemble C3a activation than C5a activation.

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).


Derivation of ligands for the complement C3a receptor from the C-terminus of C5a.

Halai R, Bellows-Peterson ML, Branchett W, Smadbeck J, Kieslich CA, Croker DE, Cooper MA, Morikis D, Woodruff TM, Floudas CA, Monk PN - Eur. J. Pharmacol. (2014)

xCELLigence response profiles for C3a and C5a at 100 nM, and peptides 20, 31, 47, 49 and 54 at 100 μM. A two-peak profile is evident for C5a, whereas a single peak profile is apparent for C3a. Peptide profiles more closely resemble C3a activation than C5a activation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4263610&req=5

f0010: xCELLigence response profiles for C3a and C5a at 100 nM, and peptides 20, 31, 47, 49 and 54 at 100 μM. A two-peak profile is evident for C5a, whereas a single peak profile is apparent for C3a. Peptide profiles more closely resemble C3a activation than C5a activation.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.

Show MeSH
Related in: MedlinePlus