title: Signal relay by CC chemokine receptor 2 (CCR2) and formylpeptide receptor 2 (Fpr2) in the recruitment of monocyte-derived dendritic cells in allergic airway inflammation.
abstract: Chemoattractant receptors regulate leukocyte accumulation at sites of inflammation. In allergic airway inflammation, although a chemokine receptor CCR2 was implicated in mediating monocyte-derived dendritic cell (DC) recruitment into the lung, we previously also discovered reduced accumulation of DCs in the inflamed lung in mice deficient in formylpeptide receptor Fpr2 (Fpr2(-/-)). We therefore investigated the role of Fpr2 in the trafficking of monocyte-derived DCs in allergic airway inflammation in cooperation with CCR2. We report that in allergic airway inflammation, CCR2 mediated the recruitment of monocyte-derived DCs to the perivascular region, and Fpr2 was required for further migration of the cells into the bronchiolar area. We additionally found that the bronchoalveolar lavage liquid from mice with airway inflammation contained both the CCR2 ligand CCL2 and an Fpr2 agonist CRAMP. Furthermore, similar to Fpr2(-/-) mice, in the inflamed airway of CRAMP(-/-) mice, DC trafficking into the peribronchiolar areas was diminished. Our study demonstrates that the interaction of CCR2 and Fpr2 with their endogenous ligands sequentially mediates the trafficking of DCs within the inflamed lung.
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research.
authors.forename: Mingyong
authors.initials: M
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research.
authors.forename: Teizo
authors.initials: T
authors.lastname: Yoshimura
authors.affiliation: SAIC-Frederick, Frederick, Maryland 21702.
authors.forename: Wanghua
authors.initials: W
authors.lastname: Gong
authors.affiliation: Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Le
authors.affiliation: Mouse Cancer Genetics Program, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702.
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research. Electronic address: wangji@mail.nih.gov.
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001249:Asthma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054804:Cathelicidins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D044042:Receptors, Formyl Peptide; C481578:formyl peptide receptor 2, mouse
keywords: CCR2; Chemokines; Chemotaxis; Dendritic Cells; Fpr2; Lung; Monocytes; Peribronchiole Region; Perivascular Region