title: The roles of a ribosomal protein S19 polymer in a mouse model of carrageenan-induced acute pleurisy.
abstract: C5-deficient mice usually present moderate neutrophil activation during the initiation phase of acute inflammation. Conversely, C5a receptor (C5aR)-deficient mice show unusually excessive activation of neutrophils. We identified the ribosomal protein S19 (RP S19) polymer, which is cross-linked at Lys122 and Gln137 by transglutaminases in apoptotic neutrophils, as a second C5aR ligand during the resolution phase of acute inflammation. The RP S19 polymer promotes apoptosis via the neutrophil C5aR and phagocytosis via the macrophage C5aR. To confirm the roles of the RP S19 polymer, we employed a carrageenan-induced acute pleurisy mouse model using C57BL/6J mice with a knock-in of the Gln137Glu mutant RP S19 gene and replaced the RP S19 polymer with either an S-tagged C5a/RP S19 recombinant protein or the RP S19122-145peptide monomer and dimer (as functional C5aR agonists/antagonists) and the RP S19122-145peptide trimer (as a functional C5aR antagonist). Neutrophils and macrophages were still present in the thoracic cavities of the knock-in mice at 24h and 7days after carrageenan injection, respectively. Knock-in mice showed structural organization and severe hemorrhaging from the surrounding small vessels of the alveolar walls in the lung parenchyma. In contrast to the RP S19122-145peptide monomer and trimer, the simultaneous presence of S-tagged C5a/RP S19 and the RP S19122-145peptide dimer completely improved the physiological and pathological acute inflammatory cues. The RP S19 polymer, especially the dimer, appears to play a role at the resolution phase of carrageenan-induced acute pleurisy in C57BL/6J model mice.
authors.affiliation: Department of Pathology, Hyogo College of Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamanegi
authors.affiliation: Laboratory of Protein Organic Chemistry, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kawakami
authors.affiliation: Department of Pathology, Hyogo College of Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Department of Orthopedic Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kumanishi
authors.affiliation: Department of Orthopedic Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Futani
authors.affiliation: Department of Pathology, Hyogo College of Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nakasho
authors.affiliation: Department of Pathology, Hyogo College of Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: hi-nishiura@hyo-med.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishiura
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002351:Carrageenan / Q000009:adverse effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D015936:Complement C5a / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D044087:Receptor, Anaphylatoxin C5a / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011108:Polymers; D044087:Receptor, Anaphylatoxin C5a; D012269:Ribosomal Proteins; C040343:ribosomal protein S19; D015936:Complement C5a; D002351:Carrageenan
keywords: Antagonist/agonist; C5a receptor; Inflammation; Macrophages; Neutrophils; Ribosomal protein S19