THE C5A CHEMOATTRACTANT RECEPTOR MEDIATES MUCOSAL DEFENSE TO INFECTION

A FAMILY of G-protein-coupled chemoattractant receptors is known to me diate the transport and activation of neutrophils and macrophages. Thi s family includes receptors for chemokines, such as interleukin-8, bac terial formylated peptides, platelet-activating factor, leukotriene B4 , and the complement anaphylatoxins(1-3). The apparent redundancy of t hese 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 c omparison to their wild-type littermates, were unable to clear intrapu lmonary-instilled Pseudomonas aeruginosa, despite a marked increase in neutrophil influx, and succumbed to pneumonia, These C5a-receptor-def icient mice challenged with sublethal inocula of Pseudomonas become su perinfected with secondary bacterial strains. We conclude that the C5a receptor has a non-redundant function, and is required for mucosal ho st defence in the lung.