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The C5a chemoattractant receptor mediates mucosal defence to infection

Nature volume 383, pages 8689 (05 September 1996) | Download Citation

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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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  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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https://doi.org/10.1038/383086a0

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