title: Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection.
abstract: The N-terminal truncated form of a protein synthesis enzyme, tryptophanyl-tRNA synthetase (mini-WRS), is secreted as an angiostatic ligand. However, the secretion and function of the full-length WRS (FL-WRS) remain unknown. Here, we report that the FL-WRS, but not mini-WRS, is rapidly secreted upon pathogen infection to prime innate immunity. Blood levels of FL-WRS were increased in sepsis patients, but not in those with sterile inflammation. FL-WRS was secreted from monocytes and directly bound to macrophages via a toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex to induce phagocytosis and chemokine production. Administration of FL-WRS into Salmonella typhimurium-infected mice reduced the levels of bacteria and improved mouse survival, whereas its titration with the specific antibody aggravated the infection. The N-terminal 154-amino-acid eukaryote-specific peptide of WRS was sufficient to recapitulate FL-WRS activity and its interaction mode with TLR4-MD2 is now suggested. Based on these results, secretion of FL-WRS appears to work as a primary defence system against infection, acting before full activation of innate immunity.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Young Ha
authors.initials: YH
authors.lastname: Ahn
authors.affiliation: College of Korean Medicine, Daejeon University, Daejeon 34520, Republic of Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Park
authors.affiliation: College of Korean Medicine, Daejeon University, Daejeon 34520, Republic of Korea.
authors.forename: Jeong June
authors.initials: JJ
authors.lastname: Choi
authors.affiliation: College of Korean Medicine, Daejeon University, Daejeon 34520, Republic of Korea.
authors.forename: Bo-Kyung
authors.initials: BK
authors.lastname: Park
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Rhee
authors.affiliation: Medicinal Bioconvergence Research Center, Seoul National University, Suwon 16229, Republic of Korea.
authors.forename: Eunjoo
authors.initials: E
authors.lastname: Kang
authors.affiliation: Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 34113, Republic of Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea.
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Inn
authors.affiliation: Divison of Rheumatology, Department of Internal Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.|Institute of Allergy, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Park
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.|Institute of Allergy, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.|Institute of Allergy, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.|Institute of Allergy, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Medicinal Bioconvergence Research Center, Seoul National University, Suwon 16229, Republic of Korea.
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Kwon
authors.affiliation: Departments of Bioinspired Science and Life Science, Ewha Womans University, Seoul 03760, Republic of Korea.
authors.forename: Hyunbo
authors.initials: H
authors.lastname: Shim
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Han
authors.affiliation: Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Pilhan
authors.initials: P
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.|Korea Chemical Bank, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
authors.forename: Joo-Youn
authors.initials: JY
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Korea University, Sejong 30019, Republic of Korea.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Jeon
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Huh
authors.affiliation: College of Korean Medicine, Daejeon University, Daejeon 34520, Republic of Korea.
authors.forename: Mirim
authors.initials: M
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.|Medicinal Bioconvergence Research Center, Seoul National University, Suwon 16229, Republic of Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology* / Q000473:pathology; D058491:Bacterial Load; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D010587:Phagocytosis; D012481:Salmonella Infections, Animal; D012486:Salmonella typhimurium / Q000302:isolation & purification; D018805:Sepsis / Q000276:immunology / Q000473:pathology; D016019:Survival Analysis; D014369:Tryptophan-tRNA Ligase / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
chemical_list: D018925:Chemokines; D007155:Immunologic Factors; D014369:Tryptophan-tRNA Ligase