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The C5a chemoattractant receptor mediates mucosal defence to infection

Nature volume 383, pages 86–89 (1996)Cite this article

Abstract

A FAMILY of G-protein-eoupled chemoattractant receptors is known to mediate the transport and activation of neutrophils and macrophages. This family includes receptors for chemokines, such as interleukin-8, bacterial formylated peptides, platelet-activating factor, leukotriene B4, and the complement anaphyla-toxins1–3. The apparent redundancy of these receptors suggests that they have an important underlying role in host defence. To isolate the contribution of particular molecules, we disrupted a gene that encodes a single chemoattractant receptor. Here we show that mice deficient in the chemoattractant C5a receptor, in comparison to their wild-type littermates, were unable to clear intrapulmonary-instilled Pseudomonas aeruginosa, despite a marked increase in neutrophil influx, and succumbed to pneumonia. These C5a-receptor-deficient mice challenged with sub-lethal inocula of Pseudomonas become superinfected with secondary bacterial strains. We conclude that the C5a receptor has a non-redundant function, and is required for mucosal host defence in the lung.

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References

  1. Gerard, N. P. & Gerard, C. Nature 349, 614–617 (1991).

    Article  ADS  CAS  Google Scholar 

  2. Gerard, C. & Gerard, N. P. Annu. Rev. Immunol. 12, 775–808 (1994).

    Article  CAS  Google Scholar 

  3. Cacalano, G. et al. Science 265, 682–684 (1994).

    Article  ADS  CAS  Google Scholar 

  4. Gerard, C. et al. J. Immunol. 149, 2600–2606 (1992).

    CAS  PubMed  Google Scholar 

  5. Haviland, D. L. et al. J. Immunol. 154, 1861–1869 (1995).

    CAS  PubMed  Google Scholar 

  6. Kudoh, I., Wiener-Kronish, J. P., Hashimoto, S., Pittet, J. F. & Frank, D. Am. J. Physiol. 267, 551–556 (1994).

    Google Scholar 

  7. Williams, J. C., Lucas, B. J., Knee, C., Renzetti, M. & Donahue, J. Exp. Lung. Res. 18, 155–171 (1992).

    Article  CAS  Google Scholar 

  8. Frenette, P. S., Mayadas, T. N., Rayburn, H., Hynes, R. O. & Wagner, D. D. Cell 84, 563–574 (1996).

    Article  CAS  Google Scholar 

  9. Czuprynski, C. J., Henson, P. M. & Campbell, P. A. J. Leukoc. Biol. 35, 193–208 (1984).

    Article  CAS  Google Scholar 

  10. Mosser, D. M. Immunol. Ser. 60, 99–114 (1994).

    CAS  PubMed  Google Scholar 

  11. Berger, M., Sorensen, R. U., Tosi, M. F., Dearborn, D. G. & Döring, G. J. Clin. Invest. 84, 1302–1313 (1989).

    Article  CAS  Google Scholar 

  12. Hornick, D. B. & Fick, R. B. J. J. Clin. Invest. 86, 1285–1292 (1990).

    Article  CAS  Google Scholar 

  13. Larsen, G. L., Mitchell, B. C., Harper, T. B. & Henson, P. M. Am. Rev. Resp. Dis. 126, 306–311 (1982).

    CAS  PubMed  Google Scholar 

  14. Toews, G. B., Vial, W. C. & Hansen, E. J. Infect. Immun. 50, 207–212 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Cerquetti, M. C., Sordelli, D. O., Bellanti, J. A. & Hooke, A. M. Infect. Immun. 52, 853–857 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Bozic, C. R. et al. J. Immunol. 154, 6048–6057 (1995).

    CAS  PubMed  Google Scholar 

  17. Bradley, P. P., Priebat, D. A., Christensen, R. D. & Rothstein, G. J. Invest. Dermatol. 78, 206–213 (1982).

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Ina Sue Perlmutter Cystic Fibrosis Laboratory, Children's Hospital, Brigham and Women's Hospital, the Center for Blood Research, and the Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Uta E. Höpken, Bao Lu, Norma P. Gerard & Craig Gerard

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  1. Uta E. Höpken
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  2. Bao Lu
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  3. Norma P. Gerard
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  4. Craig Gerard
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Höpken, U., Lu, B., Gerard, N. et al. The C5a chemoattractant receptor mediates mucosal defence to infection. Nature 383, 86–89 (1996). https://doi.org/10.1038/383086a0

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