title: Identification of FAM3D as a new endogenous chemotaxis agonist for the formyl peptide receptors.
abstract: The family with sequence similarity 3 (FAM3) gene family is a cytokine-like gene family with four members FAM3A, FAM3B, FAM3C and FAM3D. In this study, we found that FAM3D strongly chemoattracted human peripheral blood neutrophils and monocytes. To identify the FAM3D receptor, we used chemotaxis, receptor internalization, Ca(2+) flux and radioligand-binding assays in FAM3D-stimulated HEK293 cells that transiently expressed formyl peptide receptor (FPR)1 or FPR2 to show that FAM3D was a high affinity ligand of these receptors, both of which were highly expressed on the surface of neutrophils, and monocytes and macrophages. After being injected into the mouse peritoneal cavity, FAM3D chemoattracted CD11b+ Ly6G+ neutrophils in a short time. In response to FAM3D stimulation, phosphorylated ERK1/2 and phosphorylated p38 MAPK family proteins were upregulated in the mouse neutrophils, and this increase was inhibited upon treatment with an inhibitor of FPR1 or FPR2. FAM3D has been reported to be constitutively expressed in the gastrointestinal tract. We found that FAM3D expression increased significantly during colitis induced by dextran sulfate sodium. Taken together, we propose that FAM3D plays a role in gastrointestinal homeostasis and inflammation through its receptors FPR1 and FPR2.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Enquan
authors.initials: E
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Pei
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Dixin
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Can
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China Center for Human Disease Genomics, Peking University, Beijing 100191, China.
authors.forename: Pingzhang
authors.identifier: 0000-0001-5224-6692
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: She
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Center for Human Disease Genomics, Peking University, Beijing 100191, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Mo
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China Center for Human Disease Genomics, Peking University, Beijing 100191, China.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China Center for Human Disease Genomics, Peking University, Beijing 100191, China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China Center for Human Disease Genomics, Peking University, Beijing 100191, China yw@bjmu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002633:Chemotaxis; D003092:Colitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D044042:Receptors, Formyl Peptide / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; C553191:FAM3D protein, human; C580702:FAM3D protein, mouse; C469986:FPR1 protein, human; C105101:FPR2 protein, human; C469988:Fpr1 protein, mouse; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C481578:formyl peptide receptor 2, mouse; D016264:Dextran Sulfate; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Colitis; FAM3D; FPR1; FPR2; Neutrophils