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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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Related in: MedlinePlus

Identification of hits and target on HMDM using the xCELLigence (a) initial screen of 61 peptides at 8 μM on HMDM (n=4–6). Asterisk indicates P<0.001. Bars are shaded according to peptide length (see Supplementary Table 2), (b) dose–response curves for peptides on HMDM (n=3–5), (c) dose-dependent antagonism of response using C3a receptor antagonist SB 290157 (SB) when agonized with the EC50 concentrations of hits (n=3–5), and (d) dose-dependent antagonism of response using C5a1 antagonist PMX53 when agonized with the EC50 concentrations of hits (n=3–5).
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f0005: Identification of hits and target on HMDM using the xCELLigence (a) initial screen of 61 peptides at 8 μM on HMDM (n=4–6). Asterisk indicates P<0.001. Bars are shaded according to peptide length (see Supplementary Table 2), (b) dose–response curves for peptides on HMDM (n=3–5), (c) dose-dependent antagonism of response using C3a receptor antagonist SB 290157 (SB) when agonized with the EC50 concentrations of hits (n=3–5), and (d) dose-dependent antagonism of response using C5a1 antagonist PMX53 when agonized with the EC50 concentrations of hits (n=3–5).

Mentions: The 61 peptides, initially dissolved in dimethyl sulfoxide (DMSO) at 10 mM, were screened at a single dose of 8 μM on HMDM using an impedance based label-free system, the xCELLigence; DMSO at <0.5% was found to have no effects in this assay. Fig. 1A shows the identification of 5 significant hits (P<0.001), peptides 20, 31, 47, 48 and 54. Peptide 49 was identified as a potential hit from independent data (data not shown) despite not evoking a response in the initial screen and so was retested at the full dose range along with the five identified hits (see Fig. 1B). Interestingly, a full dose response could not be obtained for peptide 48 (data not shown). However, peptide 49 showed weak activity, despite failing in the initial single dose screen. The EC50 of the hits has been summarized in Table 1.


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)

Identification of hits and target on HMDM using the xCELLigence (a) initial screen of 61 peptides at 8 μM on HMDM (n=4–6). Asterisk indicates P<0.001. Bars are shaded according to peptide length (see Supplementary Table 2), (b) dose–response curves for peptides on HMDM (n=3–5), (c) dose-dependent antagonism of response using C3a receptor antagonist SB 290157 (SB) when agonized with the EC50 concentrations of hits (n=3–5), and (d) dose-dependent antagonism of response using C5a1 antagonist PMX53 when agonized with the EC50 concentrations of hits (n=3–5).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4263610&req=5

f0005: Identification of hits and target on HMDM using the xCELLigence (a) initial screen of 61 peptides at 8 μM on HMDM (n=4–6). Asterisk indicates P<0.001. Bars are shaded according to peptide length (see Supplementary Table 2), (b) dose–response curves for peptides on HMDM (n=3–5), (c) dose-dependent antagonism of response using C3a receptor antagonist SB 290157 (SB) when agonized with the EC50 concentrations of hits (n=3–5), and (d) dose-dependent antagonism of response using C5a1 antagonist PMX53 when agonized with the EC50 concentrations of hits (n=3–5).
Mentions: The 61 peptides, initially dissolved in dimethyl sulfoxide (DMSO) at 10 mM, were screened at a single dose of 8 μM on HMDM using an impedance based label-free system, the xCELLigence; DMSO at <0.5% was found to have no effects in this assay. Fig. 1A shows the identification of 5 significant hits (P<0.001), peptides 20, 31, 47, 48 and 54. Peptide 49 was identified as a potential hit from independent data (data not shown) despite not evoking a response in the initial screen and so was retested at the full dose range along with the five identified hits (see Fig. 1B). Interestingly, a full dose response could not be obtained for peptide 48 (data not shown). However, peptide 49 showed weak activity, despite failing in the initial single dose screen. The EC50 of the hits has been summarized in Table 1.

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