Anaphylatoxin receptor promiscuity for commonly used complement C5a peptide agonists.
Xaria X Li1, Richard J Clark1, Trent M Woodruff1
1School of Biomedical Sciences, The University of Queensland, St Lucia 4072 Australia.
International Immunopharmacology
|August 28, 2021
Summary
Commonly used C5a agonists EP54, EP67, and C5apep lack selectivity for the C5a receptor (C5aR1). These peptides activate other complement receptors, limiting their use as research tools for C5a/C5aR studies.
Area of Science:
- Immunology
- Pharmacology
Background:
- The complement system is crucial for innate immunity, generating anaphylatoxins C3a and C5a.
- These anaphylatoxins signal through seven-transmembrane receptors: C3aR, C5aR1, and C5aR2.
- C5aR1 is a key inflammatory mediator and a target for drug development.
Purpose of the Study:
- To characterize the selectivity of commonly used C5a agonists EP54, EP67, and C5apep.
- To evaluate their activity at human C5aR1, C5aR2, and C3aR.
Main Methods:
- Signaling assays were performed in transfected cell lines.
- Human primary macrophages were utilized for further characterization.
Main Results:
- None of the tested compounds (EP54, EP67, C5apep) demonstrated selectivity for human C5aR1.
- EP54 and EP67 acted as potent, full agonists for C3aR.
- EP54 and C5apep partially activated human C5aR2.
Conclusions:
- The tested C5a agonists lack receptor selectivity.
- Caution is advised when using EP54, EP67, and C5apep as C5a surrogates in research.
- These findings impact the interpretation of studies involving these widely used complement research tools.
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