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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

Therapeutic potential of histone H1-targeted SSV mAb on allergic rhinitis-like symptoms.Mice were immunized with OVA/alum (n = 9). SSV mAb (100 μg, n = 4) or isotype IgG1 (100 μg, n = 5) was then intraperitoneally administered before daily OVA nasal challenge. To evaluate allergic rhinitis-like symptoms, the instances of sneezing (A) and nasal rubbing (data not shown) were counted for 5 minutes immediately after OVA nasal challenge. *, P<0.05 versus the isotype IgG1-injected group. (B) Representative sections of the nasal septal mucosa in isotype IgG1 or SSV mAb-injected group. Eosinophils (left: H&E staining) and mast cells (right: toluidine blue staining) (shown by arrows) were counted under a microscope at ×400 magnification. Values are presented as the mean ± S.D. **, P<0.01 versus the isotype IgG1-injected group.
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pone.0153630.g005: Therapeutic potential of histone H1-targeted SSV mAb on allergic rhinitis-like symptoms.Mice were immunized with OVA/alum (n = 9). SSV mAb (100 μg, n = 4) or isotype IgG1 (100 μg, n = 5) was then intraperitoneally administered before daily OVA nasal challenge. To evaluate allergic rhinitis-like symptoms, the instances of sneezing (A) and nasal rubbing (data not shown) were counted for 5 minutes immediately after OVA nasal challenge. *, P<0.05 versus the isotype IgG1-injected group. (B) Representative sections of the nasal septal mucosa in isotype IgG1 or SSV mAb-injected group. Eosinophils (left: H&E staining) and mast cells (right: toluidine blue staining) (shown by arrows) were counted under a microscope at ×400 magnification. Values are presented as the mean ± S.D. **, P<0.01 versus the isotype IgG1-injected group.

Mentions: To further evaluate the therapeutic effect of SSV mAb on mast cell-mediated allergic responses in vivo, SSV mAb or IgG1 isotype control (100 μg/mouse) was intraperitoneally injected into the OVA/alum-sensitized mice before the daily nasal challenge with OVA (1 mg). As shown in Fig 5A, SSV mAb significantly ameliorated the symptoms of OVA-induced sneezing and nasal rubbing (data not shown) compared with the isotype control. Pathological observation demonstrated the infiltration of eosinophils and mast cells in the nasal mucosa of isotype control group, while SSV mAb markedly reduced those infiltration (Fig 5B).


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)

Therapeutic potential of histone H1-targeted SSV mAb on allergic rhinitis-like symptoms.Mice were immunized with OVA/alum (n = 9). SSV mAb (100 μg, n = 4) or isotype IgG1 (100 μg, n = 5) was then intraperitoneally administered before daily OVA nasal challenge. To evaluate allergic rhinitis-like symptoms, the instances of sneezing (A) and nasal rubbing (data not shown) were counted for 5 minutes immediately after OVA nasal challenge. *, P<0.05 versus the isotype IgG1-injected group. (B) Representative sections of the nasal septal mucosa in isotype IgG1 or SSV mAb-injected group. Eosinophils (left: H&E staining) and mast cells (right: toluidine blue staining) (shown by arrows) were counted under a microscope at ×400 magnification. Values are presented as the mean ± S.D. **, P<0.01 versus the isotype IgG1-injected group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0153630.g005: Therapeutic potential of histone H1-targeted SSV mAb on allergic rhinitis-like symptoms.Mice were immunized with OVA/alum (n = 9). SSV mAb (100 μg, n = 4) or isotype IgG1 (100 μg, n = 5) was then intraperitoneally administered before daily OVA nasal challenge. To evaluate allergic rhinitis-like symptoms, the instances of sneezing (A) and nasal rubbing (data not shown) were counted for 5 minutes immediately after OVA nasal challenge. *, P<0.05 versus the isotype IgG1-injected group. (B) Representative sections of the nasal septal mucosa in isotype IgG1 or SSV mAb-injected group. Eosinophils (left: H&E staining) and mast cells (right: toluidine blue staining) (shown by arrows) were counted under a microscope at ×400 magnification. Values are presented as the mean ± S.D. **, P<0.01 versus the isotype IgG1-injected group.
Mentions: To further evaluate the therapeutic effect of SSV mAb on mast cell-mediated allergic responses in vivo, SSV mAb or IgG1 isotype control (100 μg/mouse) was intraperitoneally injected into the OVA/alum-sensitized mice before the daily nasal challenge with OVA (1 mg). As shown in Fig 5A, SSV mAb significantly ameliorated the symptoms of OVA-induced sneezing and nasal rubbing (data not shown) compared with the isotype control. Pathological observation demonstrated the infiltration of eosinophils and mast cells in the nasal mucosa of isotype control group, while SSV mAb markedly reduced those infiltration (Fig 5B).

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