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An Anti-inflammatory Function for the Complement Anaphylatoxin C5a-binding Protein, C5L2
Open accessAbstract
C5L2 is an enigmatic serpentine receptor that is co-expressed with the C5a receptor on many cells including polymorphonuclear neutrophils. The apparent absence of coupling of C5L2 with G proteins suggests that this receptor may modulate the biological activity of C5a, perhaps by acting as a decoy receptor. Alternatively, C5L2 may affect C5a function through formation of a heteromeric complex with the C5aR, or it may utilize a G protein-independent signaling pathway. Here we show that in mice bearing a targeted deletion of C5L2, the biological activity of C5a/C5a(desArg) is enhanced both in vivo and in vitro. The biological role of C5L2 thus appears to be limiting to the pro-inflammatory response to the anaphylatoxin. Accordingly, up-regulation of C5L2 may be of benefit in inflammatory states driven by C5a, including sepsis, asthma, cystic fibrosis, and chronic obstructive lung disease.
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Citations
Cited by
Harmful molecular mechanisms in sepsis
Rittirsch, D., Flierl, M. A., & Ward, P. A. (2008) · Nature Reviews Immunology · doi:10.1038/nri2402 · Cited by 1,202
Complement System Part II: Role in Immunity
Merle, N. S., Noe, R., Halbwachs-Mecarelli, L., Fremeaux-Bacchi, V., & Roumenina, L. T. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00257 · Cited by 1,051
Overview of complement activation and regulation
Noris, M., & Remuzzi, G. (2013) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2013.08.001 · Cited by 864
Bachelerie, F., Ben-Baruch, A., Burkhardt, A. M., Combadiere, C., Farber, J. M., Graham, G. J., Horuk, R., Sparre-Ulrich, A. H., Locati, M., Luster, A. D., et al. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.007724 · Cited by 850
The role of the anaphylatoxins in health and disease
Klos, A., Tenner, A. J., Johswich, K.-O., Ager, R. R., Reis, E. S., & Köhl, J. (2009) · Molecular Immunology · doi:10.1016/j.molimm.2009.04.027 · Cited by 730
Metadata
- Authors
- Gerard, N. P., Lu, B., Liu, P., Craig, S., Fujiwara, Y., Okinaga, S., & Gerard, C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 280
- Issue
- 48
- Pages
- 39677-39680
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2085445504
- Cited by
- 201
- References
- 0
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Gerard, N. P., Lu, B., Liu, P., Craig, S., Fujiwara, Y., Okinaga, S., & Gerard, C. (2005). An Anti-inflammatory Function for the Complement Anaphylatoxin C5a-binding Protein, C5L2. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.c500287200
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