F2L, a Peptide Derived from Heme-Binding Protein, Chemoattracts Mouse Neutrophils by Specifically Activating Fpr2, the Low-Affinity <i>N</i> -Formylpeptide Receptor

  • Ji-Liang Gao
    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892
  • Aude Guillabert
    Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme , Brussels ,
  • Jinyue Hu
    Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick Cancer Research and Development Center , Frederick, MD 21702
  • Yingying Le
    Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick Cancer Research and Development Center , Frederick, MD 21702
  • Eneko Urizar
    Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme , Brussels ,
  • Eva Seligman
    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892
  • Kevin J Fang
    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892
  • Xiaoning Yuan
    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892
  • Virginie Imbault
    Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme , Brussels ,
  • David Communi
    Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme , Brussels ,
  • Ji Ming Wang
    Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick Cancer Research and Development Center , Frederick, MD 21702
  • Marc Parmentier
    Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme , Brussels ,
  • Philip M Murphy
    Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892
  • Isabelle Migeotte
    Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles Campus Erasme , Brussels ,

書誌事項

公開日
2007-02-01
権利情報
  • https://academic.oup.com/pages/standard-publication-reuse-rights
DOI
  • 10.4049/jimmunol.178.3.1450
公開者
Oxford University Press (OUP)

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<jats:title>Abstract</jats:title> <jats:p>F2L (formylpeptide receptor (FPR)-like (FPRL)-2 ligand), a highly conserved acetylated peptide derived from the amino-terminal cleavage of heme-binding protein, is a potent chemoattractant for human monocytes and dendritic cells, and inhibits LPS-induced human dendritic cell maturation. We recently reported that F2L is able to activate the human receptors FPRL-1 and FPRL2, two members of the FPR family, with highest selectivity and affinity for FPRL2. To facilitate delineation of mechanisms of F2L action in vivo, we have now attempted to define its mouse receptors. This is complicated by the nonequivalence of the human and mouse FPR gene families (three vs at least eight members, respectively). When cell lines were transfected with plasmids encoding the eight mouse receptors, only the one expressing the receptor Fpr2 responded to F2L (EC50 ∼400 nM for both human and mouse F2L in both calcium flux and cAMP inhibition assays). This value is similar to F2L potency at human FPRL1. Consistent with this, mouse neutrophils, which like macrophages and dendritic cells express Fpr2, responded to human and mouse F2L in both calcium flux and chemotaxis assays with EC50 values similar to those found for Fpr2-expressing cell lines (∼500 nM). Moreover, neutrophils from mice genetically deficient in Fpr2 failed to respond to F2L. Thus, Fpr2 is a mouse receptor for F2L, and can be targeted for the study of F2L action in mouse models.</jats:p>

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