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 S19122-145 peptide monomer and dimer (as functional C5aR agonists/antagonists) and the RP S19122-145 peptide 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 S19122-145 peptide monomer and trimer, the simultaneous presence of S-tagged C5a/RP S19 and the RP S19122-145 peptide 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: Koji Yamanegi, Toru Kawakami, Naoko Yamada, Shunsuke Kumanishi, Hiroyuki Futani, Keiji Nakasho, Hiroshi Nishiura
• Journal: Immunobiology (Immunobiology) Vol. 222 Issue 5 Pg. 738-750 (05 2017) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 28190533 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier GmbH. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin G
• Polymers
• Receptor, Anaphylatoxin C5a
• Ribosomal Proteins
• ribosomal protein S19
• Complement C5a
• Carrageenan

Topics

• Animals
• Antibodies, Monoclonal (immunology, pharmacology)
• Carrageenan (adverse effects)
• Chemotaxis, Leukocyte (drug effects, immunology)
• Complement C5a (immunology, metabolism)
• Disease Models, Animal
• Immunoglobulin G (immunology, pharmacology)
• Lung (immunology, metabolism, pathology)
• Macrophages (drug effects, immunology, metabolism)
• Mice
• Mice, Transgenic
• Monocytes (drug effects, immunology, metabolism)
• Neutrophils (drug effects, immunology, metabolism)
• Phagocytosis (drug effects, immunology)
• Pleurisy (chemically induced, drug therapy, immunology, metabolism)
• Polymers (chemistry)
• Receptor, Anaphylatoxin C5a (agonists, antagonists & inhibitors, metabolism)
• Ribosomal Proteins (chemistry, genetics, immunology, pharmacology)