C5a, but not C5a-des Arg, induces upregulation of heteromer formation between complement C5a receptors C5aR and C5L2

Croker, Daniel E., Halai, Reena, Fairlie, David P. and Cooper, Matthew A. (2013) C5a, but not C5a-des Arg, induces upregulation of heteromer formation between complement C5a receptors C5aR and C5L2. Immunology and Cell Biology, 91 10: 625-633. doi:10.1038/icb.2013.48

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Author Croker, Daniel E.
Halai, Reena
Fairlie, David P.
Cooper, Matthew A.
Title C5a, but not C5a-des Arg, induces upregulation of heteromer formation between complement C5a receptors C5aR and C5L2
Journal name Immunology and Cell Biology   Check publisher's open access policy
ISSN 0818-9641
1440-1711
Publication date 2013-09-24
Year available 2013
Sub-type Article (original research)
DOI 10.1038/icb.2013.48
Volume 91
Issue 10
Start page 625
End page 633
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2014
Language eng
Formatted abstract
Receptors for C5a have an important role in innate immunity and inflammation where their expression and activation is tightly regulated. There are two known receptors for C5a: the C5a receptor (C5aR) and the C5a receptor like-2 (C5L2) receptor. Here we hypothesized that activation of C5aR might lead to heteromer formation with C5L2, as a downregulatory mechanism for C5aR signaling. To investigate this experimentally, bioluminescent resonance energy transfer (BRET) was implemented and supported by wide-field microscopy to analyze receptor localization in transfected HEK293 cells and human monocyte-derived macrophages (HMDM). BRET experiments indicated the presence of constitutive C5aR-C5L2 heteromers, where C5a, but not C5a-des Arg, was able to induce further heteromer formation, which was inhibited by a C5aR-specific antagonist. The data obtained suggest that C5aR-C5L2 can form heteromers in a process enhanced by C5a, but not by C5a-des Arg. There was also a significant difference in the levels of the anti-inflammatory cytokine IL-10 detected in HMDM following exposure to C5a compared with that seen for C5a-des Arg but no differences in the pro-inflammatory cytokines TNFα and IL-6. These subtle differences in C5a and C5a-des Arg induced receptor function may be of benefit in understanding the regulation of C5a in acute inflammation.
Keyword BRET
C5a
Interleukin-10
Inflammation
Macrophages
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Advance online publication 24 September 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 21 Nov 2013, 11:57:09 EST by Susan Allen on behalf of Institute for Molecular Bioscience