title: A novel anti-histone H1 monoclonal antibody, SSV monoclonal antibody, improves lung injury and survival in a mouse model of lipopolysaccharide-induced sepsis-like syndrome.
abstract: BACKGROUND
  Histones play important roles in both host defenses and inflammation related to microbial infection. A peptide mimotope (SSV) was identified from a novel histone H1 monoclonal antibody (16G9 mAb) that was shown to inhibit the mixed lymphocyte reaction. In the present study, an anti-SSV producing hybridoma was established. We investigated the effects of SSV mAb in a mouse acute inflammation model induced by intraperitoneal injection of lipopolysaccharide (LPS).
  
  
  METHODS
  SSV mAb was generated and characterized. Mice were treated with SSV mAb or a control IgG antibody prior to LPS injection. Evaluation of survival rate and lung tissue on histological score was performed. The levels of inflammatory cytokines and histones H1, H3, and H4 in plasma and lung tissue were measured by ELISA.
  
  
  RESULTS
  Competitive ELISA revealed that SSV mAb binds to histone H1. SSV mAb improved lung injury and prolonged the survival of LPS-injected mice. Increased levels of histones H1, H3, and H4 and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in plasma and lung tissue after LPS injection were ameliorated by SSV mAb.
  
  
  CONCLUSIONS
  SSV mAb is shown to have anti-inflammatory activity and organ-protective effects, highlighting the importance of controlling histone H1 as well as H3 and H4 levels during inflammation.
authors: Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Hasama-machi, Yufu, Oita 879-5593, Japan.
authors: Toru
authors: T
authors: Kusano
authors: Kazusa Institute for Drug Discovery, Josai International University, Chiba 283-8555, Japan.
authors: Kuei-Chen
authors: 0000-0003-1808-3468
authors: KC
authors: Chiang
authors: Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Hasama-machi, Yufu, Oita 879-5593, Japan.
authors: Masafumi
authors: M
authors: Inomata
authors: Kazusa Institute for Drug Discovery, Josai International University, Chiba 283-8555, Japan.
authors: Yayoi
authors: Y
authors: Shimada
authors: Kazusa Institute for Drug Discovery, Josai International University, Chiba 283-8555, Japan.
authors: Naoya
authors: N
authors: Ohmori
authors: Kazusa Institute for Drug Discovery, Josai International University, Chiba 283-8555, Japan.
authors: Takeshi
authors: T
authors: Goto
authors: Kazusa Institute for Drug Discovery, Josai International University, Chiba 283-8555, Japan.
authors: Shuji
authors: S
authors: Sato
authors: Iwao Hospital, Yufuin 879-5102, Japan ; Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
authors: Shigeru
authors: S
authors: Goto
authors: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
authors: Toshiaki
authors: T
authors: Nakano
authors: Department of Molecular Biotechnology, Graduate School of Advanced Science of Matter, Hiroshima University, Higashi-Hiroshima 739-8511, Japan.
authors: Seiji
authors: S
authors: Kawamoto
authors: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
authors: Yuki
authors: 0000-0001-9329-3559
authors: Y
authors: Takaoka
authors: Center for Community Medicine, Oita University Faculty of Medicine, Oita 879-5593, Japan.
authors: Norio
authors: N
authors: Shiraishi
authors: Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita 879-5593, Japan.
authors: Takayuki
authors: T
authors: Noguchi
authors: Oita University, Oita 870-1192, Japan.
authors: Seigo
authors: S
authors: Kitano
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006657:Histones / Q000037:antagonists & inhibitors* / Q000276:immunology; D008070:Lipopolysaccharides; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality*; D018805:Sepsis
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D006657:Histones; D008070:Lipopolysaccharides; D010455:Peptides
references: Infect Immun. 1993 Apr;61(4):1496-9
references: 8454355
references: Nature. 1981 Aug 27;292(5826):840-2
references: 7022223
references: J Exp Med. 1994 Apr 1;179(4):1253-9
references: 8145042
references: J Exp Med. 1996 Mar 1;183(3):949-58
references: 8642298
references: Eur J Immunol. 1996 Jul;26(7):1580-6
references: 8766564
references: Eur J Clin Invest. 1997 Jan;27(1):3-9
references: 9041370
references: J Interferon Cytokine Res. 1999 Jun;19(6):563-73
references: 10433356
references: Crit Care Med. 1999 Jul;27(7):1309-18
references: 10446825
references: Mol Immunol. 2005 Jun;42(10):1155-64
references: 15829305
references: Biomed Chromatogr. 2008 Jan;22(1):13-9
references: 17604361
references: Crit Care Med. 2008 Jan;36(1 Suppl):S9-16
references: 18158483
references: J Immunol. 2008 Feb 1;180(3):1895-902
references: 18209087
references: Transpl Immunol. 2008 May;19(2):87-92
references: 18503883
references: J Cell Biol. 2009 Jan 26;184(2):205-13
references: 19153223
references: J Immunol. 2009 Apr 1;182(7):4282-8
references: 19299727
references: Nat Med. 2009 Nov;15(11):1318-21
references: 19855397
references: Immunology. 2010 Apr;129(4):547-55
references: 20102416
references: Transplant Rev (Orlando). 2011 Jan;25(1):27-35
references: 21126661
references: PLoS One. 2011;6(1):e14525
references: 21264293
references: Transplantation. 1983 Apr;35(4):304-11
references: 6404027
references: Nature. 1986 Apr 17-23;320(6063):584-8
references: 3010124
references: Transplantation. 1986 Dec;42(6):581-7
references: 3538546
references: J Clin Invest. 1988 Apr;81(4):1162-72
references: 3258319
references: Am J Pathol. 1991 May;138(5):1097-101
references: 2024703
references: Am J Physiol. 1991 Oct;261(4 Pt 1):E457-65
references: 1928337
references: J Exp Med. 1991 Nov 1;174(5):1209-20
references: 1940799
references: N Engl J Med. 2012 May 31;366(22):2055-64
references: 22616830
references: J Trauma Acute Care Surg. 2012 Dec;73(6):1389-94
references: 23188230
references: Biochem Biophys Res Commun. 2013 Feb 8;431(2):246-52
references: 23313492
references: Clin Dev Immunol. 2013;2013:267156
references: 23690821
references: Clin Exp Immunol. 2001 Jan;123(1):62-7
references: 11167999
references: Immunity. 2001 Jun;14(6):705-14
references: 11420041
references: Shock. 2002 Sep;18(3):236-41
references: 12353924
references: Annu Rev Immunol. 1993;11:165-90
references: 8386517