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* Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612; and
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892
The prototypic formyl peptide N-formyl-Met-Leu-Phe (fMLF) is a major chemoattractant found in Escherichia coli culture supernatants and a potent agonist at human formyl peptide receptor (FPR) 1. Consistent with this, fMLF induces bactericidal functions in human neutrophils at nanomolar concentrations. However, it is a much less potent agonist for mouse FPR (mFPR) 1 and mouse neutrophils, requiring micromolar concentrations for cell activation. To determine whether other bacteria produce more potent agonists for mFPR1, we examined formyl peptides from Listeria monocytogenes and Staphylococcus aureus for their abilities to activate mouse neutrophils. A pentapeptide (N-formyl-Met-Ile-Val-Ile-Leu (fMIVIL)) from L. monocytogenes and a tetrapeptide (N-formyl-Met-Ile-Phe-Leu (fMIFL)) from S. aureus were found to induce mouse neutrophil chemotaxis at 1–10 nM and superoxide production at 10–100 nM, similar to the potency of fMLF on human neutrophils. Using transfected cell lines expressing mFPR1 and mFPR2, which are major forms of FPRs in mouse neutrophils, we found that mFPR1 is responsible for the high potency of fMIVIL and fMIFL. In comparison, activation of mFPR2 requires micromolar concentrations of the two peptides. Genetic deletion of mfpr1 resulted in abrogation of neutrophil superoxide production and degranulation in response to fMIVIL and fMIFL, further demonstrating that mFPR1 is the primary receptor for detection of these formyl peptides. In conclusion, the formyl peptides from L. monocytogenes and S. aureus are 
100-fold more potent than fMLF in activating mouse neutrophils. The ability of mFPR1 to detect bacterially derived formyl peptides indicates that this important host defense mechanism is conserved in mice.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by National Institutes of Health Grants AI033503, AI040176, and HL077806. E.L.S. is supported by a National Research Service Award/National Institutes of Health Institutional T32 Training Grant, "Lung Physiology and Pathophysiology" (T32 HL007829).
2 Address correspondence and reprint request to Dr. Richard D. Ye, Department of Pharmacology, University of Illinois, 835 South Wolcott Avenue, Chicago, IL 60612. E-mail address: yer{at}uic.edu
3 Abbreviations used in this paper: fMLF, fMet-Leu-Phe; fMIFL, N-formyl-Met-Ile-Phe-Leu; fMIVIL, N-formyl-Met-Ile-Val-Ile-Leu; FPR, formyl peptide receptor; FPRL, FPR-like; hFPR, human FPR; KO, knockout; mFPR, mouse FPR; WT, wild type.
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  R. D. Ye, F. Boulay, J. M. Wang, C. Dahlgren, C. Gerard, M. Parmentier, C. N. Serhan, and P. M. Murphy International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the Formyl Peptide Receptor (FPR) Family Pharmacol. Rev., June 1, 2009; 61(2): 119 - 161. [Abstract] [Full Text] [PDF]
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