N-formylpeptides Induce Two Distinct Concentration Optima for Mouse Neutrophil Chemotaxis by Differential Interaction with Two N-formylpeptide Receptor (FPR) Subtypes: Molecular Characterization of FPR2, a Second Mouse Neutrophil FPR

doi:10.1084/jem.190.5.741

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© The Rockefeller University Press, 0022-1007/1999/9/741/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 5, September 6, 1999 741-748

N-formylpeptides Induce Two Distinct Concentration Optima for Mouse Neutrophil Chemotaxis by Differential Interaction with Two N-formylpeptide Receptor (FPR) Subtypes: Molecular Characterization of FPR2, a Second Mouse Neutrophil FPR

Jennifer K. Hartt^a, Grant Barish^a, Philip M. Murphy^a, and Ji-Liang Gao^a
^a From the Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Correspondence to: Ji-Liang Gao, Laboratory of Host Defenses, NIAID, Bldg. 10, Rm. 11N113, National Institutes of Health, Bethesda, MD 20892. Tel:301-496-2877 Fax:301-402-4369 E-mail:jgao{at}nih.gov.

The N-formylpeptide receptor (FPR) is a G protein–coupledreceptor that mediates mammalian phagocyte chemotactic responsesto bacterial N-formylpeptides. Here we show that a mouse genenamed Fpr-rs2 encodes a second N-formylpeptide receptor subtypeselective for neutrophils which we have provisionally namedFPR2. The prototype N-formylpeptide fMLF induced calcium fluxand chemotaxis in human embryonic kidney (HEK) 293 cells stablytransfected with FPR2. The EC₅₀s, ~5 µM for calcium fluxand chemotaxis, were ~100-fold greater than the correspondingvalues for mouse FPR-transfected HEK 293 cells. Consistent withthis, fMLF induced two distinct concentration optima for chemotaxisof normal mouse neutrophils, but only the high concentrationoptimum for chemotaxis of neutrophils from FPR knockout mice.Based on these data, we hypothesize that high- and low-affinityN-formylpeptide receptors, FPR and FPR2, respectively, may functionin vivo as a relay mediating neutrophil migration through thehigh and low concentration portions of N-formylpeptide gradients.

Key Words: chemoattractant, inflammation, neutrophil, G protein–coupledreceptor, phagocyte

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