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Increased C5a receptor expression in sepsis
Open accessAbstract
Excessive production of the complement activation product C5a appears to be harmful during the development of sepsis in rodents. Little is known about the role of the C5a receptor (C5aR) and its presence in different organs during sepsis. Using the cecal ligation/puncture (CLP) model in mice, we show here that C5aR immunoreactivity was strikingly increased in lung, liver, kidney, and heart early in sepsis in both control and neutrophil-depleted mice. C5aR mRNA expression in these organs was also significantly increased during sepsis. Immunohistochemical analysis revealed patterns of increased C5aR expression in parenchymal cells in all four organs following CLP. Mice injected at the start of CLP with a blocking IgG to C5aR (alphaC5aR) showed dramatically improved survival when compared with animals receiving nonspecific IgG, as did mice injected with alphaC5a. In alphaC5aR-treated mice, serum levels of IL-6 and TNF-alpha and bacterial counts in various organs were significantly reduced during CLP when compared with control CLP animals. These studies demonstrate for the first time that C5aR is upregulated in lung, liver, kidney, and heart during the early phases of sepsis and that blockade of C5aR is highly protective from the lethal outcome of sepsis.
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Citations
Cited by
Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis
Thimmulappa, R. K. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25790 · Cited by 1,028
Update on Mechanisms of Ischemic Acute Kidney Injury
Devarajan, P. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006010017 · Cited by 1,026
Novel strategies for the treatment of sepsis
Riedemann, N. C., Guo, R.-F., & Ward, P. A. (2003) · Nature Medicine · doi:10.1038/nm0503-517 · Cited by 773
Self-citationAssociation of COVID-19 inflammation with activation of the C5a–C5aR1 axis
Carvelli, J., Demaria, O., Vély, F., Batista, L., Chouaki Benmansour, N., Fares, J., Carpentier, S., Thibult, M.-L., Morel, A., Remark, R., et al. (2020) · Nature · doi:10.1038/s41586-020-2600-6 · Cited by 526
Host–pathogen interactions in sepsis
van der Poll, T., & Opal, S. M. (2008) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70265-7 · Cited by 553
Metadata
- Authors
- Riedemann, N. C., Guo, R., Neff, T. A., Laudes, I. J., Keller, K. A., Sarma, V. J., Markiewski, M. M., Mastellos, D. C., Strey, C. W., Pierson, C. L., Lambris, J. D., Zetoune, F. S., & Ward, P. A.
- Venue
- Journal of Clinical Investigation
- Publisher
- American Society for Clinical Investigation
- Published
- 2002-07-01
- Volume
- 110
- Issue
- 1
- Pages
- 101-108
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2151486736
- Cited by
- 190
- References
- 0
- FWCI
- 11.41
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Increased C5a receptor expression in sepsis. https://app.cochat.ai/papers/10.1172/jci15409
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- Riedemann, N. C., Guo, R., Neff, T. A., Laudes, I. J., Keller, K. A., Sarma, V. J., Markiewski, M. M., Mastellos, D. C., Strey, C. W., Pierson, C. L., Lambris, J. D., Zetoune, F. S., & Ward, P. A. (2002). Increased C5a receptor expression in sepsis. Journal of Clinical Investigation. https://doi.org/10.1172/jci15409
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
