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J. Exp. Med.,
Volume 189, Number 4, February 15, 1999 657-662
By

From the * Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the N-formylpeptides derive from bacterial and mitochondrial proteins, and bind to specific receptors on mammalian phagocytes. Since binding induces chemotaxis and activation of phagocytes in vitro, it has been postulated that N-formylpeptide receptor signaling in vivo may be important in antimicrobial host defense, although direct proof has been lacking. Here we test this hypothesis in mice lacking the high affinity N-formylpeptide receptor (FPR), created by targeted
gene disruption. FPR
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, Maryland 20892
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mice developed normally, but had increased susceptibility to challenge with Listeria monocytogenes, as measured by increased mortality compared with wild-type
littermates. FPR
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mice also had increased bacterial load in spleen and liver 2 d after infection,
which is before development of a specific cellular immune response, suggesting a defect in innate immunity. Consistent with this, neutrophil chemotaxis in vitro and neutrophil mobilization into peripheral blood in vivo in response to the prototype N-formylpeptide fMLF
(formyl-methionyl-leucyl-phenylalanine) were both absent in FPR
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mice. These results indicate that FPR functions in antibacterial host defense in vivo.
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