Impact of Histone H1 on the Progression of Allergic Rhinitis and Its Suppression by Neutralizing Antibody in Mice

• Published in: PloS one 2016-04, Vol.11 (4), p.e0153630-e0153630
• Main Authors: Nakano, Toshiaki, Kamei, Rikiya, Fujimura, Takashi, Takaoka, Yuki, Hori, Ayane, Lai, Chia-Yun, Chiang, Kuei-Chen, Shimada, Yayoi, Ohmori, Naoya, Goto, Takeshi, Ono, Kazuhisa, Chen, Chao-Long, Goto, Shigeru, Kawamoto, Seiji
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Albumin; Allergens; Allergens - immunology; Allergic rhinitis; Allergies; Alum; Aluminum sulfate; Analysis; Anaphylaxis; Animals; Antibodies, Neutralizing - pharmacology; Antigens; Biology and life sciences; Biotechnology; Blockage; Blotting, Western; Care and treatment; Coinjection; Degranulation; Deoxyribonucleic acid; Disease Models, Animal; Disease Progression; DNA; DNA binding proteins; Female; Histone H1; Histones; Histones - immunology; Hospitals; Hyperreactivity; Hypersensitivity; Immune response; Immunoenzyme Techniques; Immunoglobulin E; Immunology; Inflammatory diseases; Laboratory animals; Lymphocytes; Male; Mast cells; Mast Cells - immunology; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Monoclonal antibodies; Nucleic acids; Nursing; Ovalbumin; Ovalbumin - toxicity; Passive cutaneous anaphylaxis; Passive Cutaneous Anaphylaxis - drug effects; Peptide Fragments - immunology; Proteins; R&D; Rats; Rats, Inbred Lew; Research & development; Research and Analysis Methods; Rhinitis; Rhinitis, Allergic - etiology; Rhinitis, Allergic - pathology; Rhinitis, Allergic - prevention & control; Rodents; Science; Studies; Transplants & implants
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153630

Nuclear antigens are known to trigger off innate and adaptive immune responses. Recent studies have found that the complex of nucleic acids and core histones that are derived from damaged cells may regulate allergic responses. However, no fundamental study has been performed concerning the role of linker histone H1 in mast cell-mediated type I hyperreactivity. In this study, we explored the impact of histone H1 on mast cell-mediated allergic responses both in vitro and in vivo. In the course of a bona-fide experimental allergen sensitization model upon co-injection with alum adjuvant, ovalbumin (OVA), but not PBS, induced elevated levels of circulating histone H1. Intranasal challenge with histone H1 to OVA/alum- (but not PBS/alum)-sensitized mice induced significantly severer symptoms of allergic rhinitis than those in mice sensitized and challenged with OVA. A monoclonal antibody against histone H1 not only suppressed mast cell degranulation, but also ameliorated OVA-induced nasal hyperreactivity and IgE-mediated passive cutaneous anaphylaxis. Our present data suggest that nuclear histone H1 represents an alarmin-like endogenous mediator acting on mast cells, and that its blockage has a therapeutic potential for mast cell-mediated type I hyperreactivity.