title: Formylpeptide receptors mediate rapid neutrophil mobilization to accelerate wound healing.
abstract: Wound healing is a multi-phased pathophysiological process requiring chemoattractant receptor-dependent accumulation of myeloid cells in the lesion. Two G protein-coupled formylpeptide receptors Fpr1 and Fpr2 mediate rapid neutrophil infiltration in the liver of Listeria-infected mice by sensing pathogen-derived chemotactic ligands. These receptors also recognize host-derived chemotactic peptides in inflammation and injury. Here we report the capacity of Fprs to promote the healing of sterile skin wound in mice by initiating neutrophil infiltration. We found that in normal miceneutrophils rapidly infiltrated the dermis in the wound before the production of neutrophil-specific chemokines by the injured tissue. In contrast, rapid neutrophil infiltration was markedly reduced with delayed wound closure in mice deficient in both Fprs. In addition, we detected Fpr ligand activity that chemoattracted neutrophils into the wound tissue. Our study thus demonstrates that Fprs are critical for normal healing of the sterile skin wound by mediating the first wave of neutrophil infiltration.
authors.affiliation: Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China; Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Mingyong
authors.initials: M
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Teizo
authors.initials: T
authors.lastname: Yoshimura
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America; National Center For Nanoscience and Technology, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Basic Research Program, Science Applications International Corporation-Frederick, Frederick, Maryland, United States of America.
authors.forename: Wanghua
authors.initials: W
authors.lastname: Gong
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Le
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Gao
authors.affiliation: Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.affiliation: The Center for Orthopedics, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Wang
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D044042:Receptors, Formyl Peptide / Q000502:physiology*; D012867:Skin / Q000276:immunology / Q000503:physiopathology; D014945:Wound Healing / Q000276:immunology*
chemical_list: D018925:Chemokines; C469988:Fpr1 protein, mouse; D044042:Receptors, Formyl Peptide; C481578:formyl peptide receptor 2, mouse