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

Nakano T, Kamei R, Fujimura T, Takaoka Y, Hori A, Lai CY, Chiang KC, Shimada Y, Ohmori N, Goto T, Ono K, Chen CL, Goto S, Kawamoto S - PLoS ONE (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Serum OVA-specific antibody titer.Peripheral blood was obtained before OVA immunization and after final OVA nasal challenge, and serum was collected (SSV mAb (n = 4) or isotype IgG1 (n = 5)). Serum OVA-specific IgE (A), IgG1 (B) and IgG2a (C) titers were determined by ELISA. Each symbol indicates an individual mouse, and bars show the mean values. NS: not significant.
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pone.0153630.g006: Serum OVA-specific antibody titer.Peripheral blood was obtained before OVA immunization and after final OVA nasal challenge, and serum was collected (SSV mAb (n = 4) or isotype IgG1 (n = 5)). Serum OVA-specific IgE (A), IgG1 (B) and IgG2a (C) titers were determined by ELISA. Each symbol indicates an individual mouse, and bars show the mean values. NS: not significant.

Mentions: To explore the therapeutic impact of SSV mAb on OVA-specific immune responses, we determined the OVA-specific immunoglobulin levels before immunization and after the final nasal challenge. As shown in Fig 6, there was no significant effect of SSV mAb on OVA-specific IgG1, IgG2a, and IgE responses.


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

Nakano T, Kamei R, Fujimura T, Takaoka Y, Hori A, Lai CY, Chiang KC, Shimada Y, Ohmori N, Goto T, Ono K, Chen CL, Goto S, Kawamoto S - PLoS ONE (2016)

Serum OVA-specific antibody titer.Peripheral blood was obtained before OVA immunization and after final OVA nasal challenge, and serum was collected (SSV mAb (n = 4) or isotype IgG1 (n = 5)). Serum OVA-specific IgE (A), IgG1 (B) and IgG2a (C) titers were determined by ELISA. Each symbol indicates an individual mouse, and bars show the mean values. NS: not significant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835108&req=5

pone.0153630.g006: Serum OVA-specific antibody titer.Peripheral blood was obtained before OVA immunization and after final OVA nasal challenge, and serum was collected (SSV mAb (n = 4) or isotype IgG1 (n = 5)). Serum OVA-specific IgE (A), IgG1 (B) and IgG2a (C) titers were determined by ELISA. Each symbol indicates an individual mouse, and bars show the mean values. NS: not significant.
Mentions: To explore the therapeutic impact of SSV mAb on OVA-specific immune responses, we determined the OVA-specific immunoglobulin levels before immunization and after the final nasal challenge. As shown in Fig 6, there was no significant effect of SSV mAb on OVA-specific IgG1, IgG2a, and IgE responses.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus