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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

Induction of allergic rhinitis-like symptoms by intranasal challenge with histone H1 in OVA/alum-sensitized mice.(A) The instance of sneezing was counted for 5 minutes immediately after calf thymus histone H1 (0.4 mg), OVA (0.4 mg) or PBS nasal challenge. *, P<0.05, **, P<0.01 versus the OVA/alum-sensitized and PBS-challenged group. #, P<0.05 versus the OVA/alum-sensitized and OVA-challenged group. (B) Representative sections of the nasal septal mucosa in OVA/alum-sensitized and PBS or histone H1-challenged group (n = 4 per 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 OVA/alum-sensitized and PBS-challenged group.
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pone.0153630.g002: Induction of allergic rhinitis-like symptoms by intranasal challenge with histone H1 in OVA/alum-sensitized mice.(A) The instance of sneezing was counted for 5 minutes immediately after calf thymus histone H1 (0.4 mg), OVA (0.4 mg) or PBS nasal challenge. *, P<0.05, **, P<0.01 versus the OVA/alum-sensitized and PBS-challenged group. #, P<0.05 versus the OVA/alum-sensitized and OVA-challenged group. (B) Representative sections of the nasal septal mucosa in OVA/alum-sensitized and PBS or histone H1-challenged group (n = 4 per 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 OVA/alum-sensitized and PBS-challenged group.

Mentions: To explore the pathophysiological role of OVA/alum sensitization-induced histone H1 in the model of allergic rhinitis, a daily intranasal administration of calf thymus histone H1 (0.4 mg) was performed after OVA/alum sensitization. As shown in Fig 2A, histone H1 significantly induced symptoms of allergic rhinitis such as sneezing and nasal rubbing (data not shown), and the frequency of sneezing was higher after histone H1 challenge than it was after OVA (0.4 mg) challenge. However, histone H1 failed to induce allergic rhinitis in PBS/alum-sensitized mice, suggesting the involvement of histone H1 in mast cell-mediated allergic responses in the presence of elevating total/OVA-specific IgE. Pathological evidence demonstrated the damage of nasal epithelium and infiltration of eosinophils and mast cells by histone H1 as compared with negative control PBS (Fig 2B).


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)

Induction of allergic rhinitis-like symptoms by intranasal challenge with histone H1 in OVA/alum-sensitized mice.(A) The instance of sneezing was counted for 5 minutes immediately after calf thymus histone H1 (0.4 mg), OVA (0.4 mg) or PBS nasal challenge. *, P<0.05, **, P<0.01 versus the OVA/alum-sensitized and PBS-challenged group. #, P<0.05 versus the OVA/alum-sensitized and OVA-challenged group. (B) Representative sections of the nasal septal mucosa in OVA/alum-sensitized and PBS or histone H1-challenged group (n = 4 per 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 OVA/alum-sensitized and PBS-challenged group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0153630.g002: Induction of allergic rhinitis-like symptoms by intranasal challenge with histone H1 in OVA/alum-sensitized mice.(A) The instance of sneezing was counted for 5 minutes immediately after calf thymus histone H1 (0.4 mg), OVA (0.4 mg) or PBS nasal challenge. *, P<0.05, **, P<0.01 versus the OVA/alum-sensitized and PBS-challenged group. #, P<0.05 versus the OVA/alum-sensitized and OVA-challenged group. (B) Representative sections of the nasal septal mucosa in OVA/alum-sensitized and PBS or histone H1-challenged group (n = 4 per 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 OVA/alum-sensitized and PBS-challenged group.
Mentions: To explore the pathophysiological role of OVA/alum sensitization-induced histone H1 in the model of allergic rhinitis, a daily intranasal administration of calf thymus histone H1 (0.4 mg) was performed after OVA/alum sensitization. As shown in Fig 2A, histone H1 significantly induced symptoms of allergic rhinitis such as sneezing and nasal rubbing (data not shown), and the frequency of sneezing was higher after histone H1 challenge than it was after OVA (0.4 mg) challenge. However, histone H1 failed to induce allergic rhinitis in PBS/alum-sensitized mice, suggesting the involvement of histone H1 in mast cell-mediated allergic responses in the presence of elevating total/OVA-specific IgE. Pathological evidence demonstrated the damage of nasal epithelium and infiltration of eosinophils and mast cells by histone H1 as compared with negative control PBS (Fig 2B).

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