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The C5a chemoattractant receptor mediates mucosal defence to infection

Naturevolume 383pages8689 (1996) | Download Citation



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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  1. 1

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

  2. 2

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

  3. 3

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

  4. 4

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

  5. 5

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

  6. 6

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

  7. 7

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

  8. 8

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

  9. 9

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

  10. 10

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

  11. 11

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

  12. 12

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

  13. 13

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

  14. 14

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

  15. 15

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

  16. 16

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

  17. 17

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

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  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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