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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

Effects of histone H1-targeted SSV mAb on circulating and local levels of histone H1.(A) Circulating histone H1 levels before nasal challenge (after 2nd OVA sensitization) and after final nasal challenge with OVA were measured by ELISA. Data are represented as the mean induction ratio after nasal challenge ± S.D. NS: not significant. (B) Local expression of histone H1 in the nasal mucosa was detected by IHC staining. Eosinophils (H&E staining), mast cells (toluidine blue staining) and histone H1 (IHC staining) were detected in the serial sections (×400 magnification). Histone H1 was detected in the granules of eosinophils and mast cells located in the epithelial zone of nasal mucosa in isotype IgG1 group, while SSV mAb significantly suppressed the local expression of histone H1 in the nasal mucosa.
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pone.0153630.g008: Effects of histone H1-targeted SSV mAb on circulating and local levels of histone H1.(A) Circulating histone H1 levels before nasal challenge (after 2nd OVA sensitization) and after final nasal challenge with OVA were measured by ELISA. Data are represented as the mean induction ratio after nasal challenge ± S.D. NS: not significant. (B) Local expression of histone H1 in the nasal mucosa was detected by IHC staining. Eosinophils (H&E staining), mast cells (toluidine blue staining) and histone H1 (IHC staining) were detected in the serial sections (×400 magnification). Histone H1 was detected in the granules of eosinophils and mast cells located in the epithelial zone of nasal mucosa in isotype IgG1 group, while SSV mAb significantly suppressed the local expression of histone H1 in the nasal mucosa.

Mentions: To explore whether SSV mAb affect the circulating level of histone H1 in OVA-sensitized and OVA-challenged mice, serum level of histone H1 was evaluated after final nasal challenge with OVA. As shown in Fig 8A, the induction ratio of circulating histone H1 after final nasal challenge as compared with 2nd OVA sensitization was no obvious difference between isotype IgG1 and SSV mAb groups. On the other hand, histone H1 was detected in the granules of eosinophils and mast cells located in the epithelial zone of nasal mucosa in isotype IgG1 group, while SSV mAb significantly suppressed the local expression of histone H1 in the nasal mucosa (Fig 8B).


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)

Effects of histone H1-targeted SSV mAb on circulating and local levels of histone H1.(A) Circulating histone H1 levels before nasal challenge (after 2nd OVA sensitization) and after final nasal challenge with OVA were measured by ELISA. Data are represented as the mean induction ratio after nasal challenge ± S.D. NS: not significant. (B) Local expression of histone H1 in the nasal mucosa was detected by IHC staining. Eosinophils (H&E staining), mast cells (toluidine blue staining) and histone H1 (IHC staining) were detected in the serial sections (×400 magnification). Histone H1 was detected in the granules of eosinophils and mast cells located in the epithelial zone of nasal mucosa in isotype IgG1 group, while SSV mAb significantly suppressed the local expression of histone H1 in the nasal mucosa.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0153630.g008: Effects of histone H1-targeted SSV mAb on circulating and local levels of histone H1.(A) Circulating histone H1 levels before nasal challenge (after 2nd OVA sensitization) and after final nasal challenge with OVA were measured by ELISA. Data are represented as the mean induction ratio after nasal challenge ± S.D. NS: not significant. (B) Local expression of histone H1 in the nasal mucosa was detected by IHC staining. Eosinophils (H&E staining), mast cells (toluidine blue staining) and histone H1 (IHC staining) were detected in the serial sections (×400 magnification). Histone H1 was detected in the granules of eosinophils and mast cells located in the epithelial zone of nasal mucosa in isotype IgG1 group, while SSV mAb significantly suppressed the local expression of histone H1 in the nasal mucosa.
Mentions: To explore whether SSV mAb affect the circulating level of histone H1 in OVA-sensitized and OVA-challenged mice, serum level of histone H1 was evaluated after final nasal challenge with OVA. As shown in Fig 8A, the induction ratio of circulating histone H1 after final nasal challenge as compared with 2nd OVA sensitization was no obvious difference between isotype IgG1 and SSV mAb groups. On the other hand, histone H1 was detected in the granules of eosinophils and mast cells located in the epithelial zone of nasal mucosa in isotype IgG1 group, while SSV mAb significantly suppressed the local expression of histone H1 in the nasal mucosa (Fig 8B).

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