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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

Enhancement and inhibition of IgE-mediated PCA reaction by histone H1 and histone H1-targeted SSV mAb.(A) PBS and anti-DNP IgE (150 ng/10 μl) with/without calf thymus histone H1 (5 μg) were intradermally injected into the left and right ears, respectively (n = 3 per group). After 24 hrs, DNP-HSA (200 μg) with evans blue solution (1%) was injected intravenously via tail vein to induce anaphylaxis. After 30 minutes, evans blue extravasation in the ears was observed. The pictures are representative of three individuals in each group. Data are representative of three independent experiments and represented as the mean ± S.D. *, P<0.05 versus the control group. (B) PBS and anti-DNP IgE (150 ng/10 μl) were intradermally injected into the left and right ears, respectively. As a sham control (n = 8), PBS was injected intradermally in both left and right ears. After 23 hrs, PBS (vehicle; n = 7), isotype IgG1 (n = 8) or SSV mAb (n = 7) was intravenously injected via tail vein. One hr later, DNP-HSA (200 μg) with evans blue solution (0.5%) was injected intravenously via tail vein to induce anaphylaxis. After 30 minutes, evans blue extravasation in the ears was observed. The pictures are representative of seven to eight individuals in each group. Each symbol indicates an individual mouse, and bars show the mean values. **, P<0.01 versus the isotype IgG1-injected group.
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pone.0153630.g004: Enhancement and inhibition of IgE-mediated PCA reaction by histone H1 and histone H1-targeted SSV mAb.(A) PBS and anti-DNP IgE (150 ng/10 μl) with/without calf thymus histone H1 (5 μg) were intradermally injected into the left and right ears, respectively (n = 3 per group). After 24 hrs, DNP-HSA (200 μg) with evans blue solution (1%) was injected intravenously via tail vein to induce anaphylaxis. After 30 minutes, evans blue extravasation in the ears was observed. The pictures are representative of three individuals in each group. Data are representative of three independent experiments and represented as the mean ± S.D. *, P<0.05 versus the control group. (B) PBS and anti-DNP IgE (150 ng/10 μl) were intradermally injected into the left and right ears, respectively. As a sham control (n = 8), PBS was injected intradermally in both left and right ears. After 23 hrs, PBS (vehicle; n = 7), isotype IgG1 (n = 8) or SSV mAb (n = 7) was intravenously injected via tail vein. One hr later, DNP-HSA (200 μg) with evans blue solution (0.5%) was injected intravenously via tail vein to induce anaphylaxis. After 30 minutes, evans blue extravasation in the ears was observed. The pictures are representative of seven to eight individuals in each group. Each symbol indicates an individual mouse, and bars show the mean values. **, P<0.01 versus the isotype IgG1-injected group.

Mentions: To explore the impact of histone H1 on PCA response in vivo, histone H1 (5 μg/10 μl) was injected intradermally both in the left and right ears. IgE-mediated PCA response induced by DNP-HSA was evaluated by the measurement of evans blue dye in the ears. As shown in Fig 4A, histone H1 without IgE sensitization (left ear) failed to induce PCA response. On the other hand, histone H1 with IgE sensitization (right ear) enhanced PCA response as compared with control group, suggesting the involvement of IgE sensitization for histone H1-mediated type I hyperreactivity. To elucidate anti-allergic mechanism of histone H1-targeted SSV mAb in vivo, SSV mAb or IgG1 isotype control (100 μg/mouse) was intravenously injected into the anti-DNP IgE-treated mice. As shown in Fig 4B, SSV mAb significantly suppressed the extravasation of evans blue compared with vehicle and isotype controls. Taken together, histone H1-targeted SSV mAb suppressed histone H1-mediated mast cell degranulation in vivo.


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)

Enhancement and inhibition of IgE-mediated PCA reaction by histone H1 and histone H1-targeted SSV mAb.(A) PBS and anti-DNP IgE (150 ng/10 μl) with/without calf thymus histone H1 (5 μg) were intradermally injected into the left and right ears, respectively (n = 3 per group). After 24 hrs, DNP-HSA (200 μg) with evans blue solution (1%) was injected intravenously via tail vein to induce anaphylaxis. After 30 minutes, evans blue extravasation in the ears was observed. The pictures are representative of three individuals in each group. Data are representative of three independent experiments and represented as the mean ± S.D. *, P<0.05 versus the control group. (B) PBS and anti-DNP IgE (150 ng/10 μl) were intradermally injected into the left and right ears, respectively. As a sham control (n = 8), PBS was injected intradermally in both left and right ears. After 23 hrs, PBS (vehicle; n = 7), isotype IgG1 (n = 8) or SSV mAb (n = 7) was intravenously injected via tail vein. One hr later, DNP-HSA (200 μg) with evans blue solution (0.5%) was injected intravenously via tail vein to induce anaphylaxis. After 30 minutes, evans blue extravasation in the ears was observed. The pictures are representative of seven to eight individuals in each group. Each symbol indicates an individual mouse, and bars show the mean values. **, P<0.01 versus the isotype IgG1-injected group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4835108&req=5

pone.0153630.g004: Enhancement and inhibition of IgE-mediated PCA reaction by histone H1 and histone H1-targeted SSV mAb.(A) PBS and anti-DNP IgE (150 ng/10 μl) with/without calf thymus histone H1 (5 μg) were intradermally injected into the left and right ears, respectively (n = 3 per group). After 24 hrs, DNP-HSA (200 μg) with evans blue solution (1%) was injected intravenously via tail vein to induce anaphylaxis. After 30 minutes, evans blue extravasation in the ears was observed. The pictures are representative of three individuals in each group. Data are representative of three independent experiments and represented as the mean ± S.D. *, P<0.05 versus the control group. (B) PBS and anti-DNP IgE (150 ng/10 μl) were intradermally injected into the left and right ears, respectively. As a sham control (n = 8), PBS was injected intradermally in both left and right ears. After 23 hrs, PBS (vehicle; n = 7), isotype IgG1 (n = 8) or SSV mAb (n = 7) was intravenously injected via tail vein. One hr later, DNP-HSA (200 μg) with evans blue solution (0.5%) was injected intravenously via tail vein to induce anaphylaxis. After 30 minutes, evans blue extravasation in the ears was observed. The pictures are representative of seven to eight individuals in each group. Each symbol indicates an individual mouse, and bars show the mean values. **, P<0.01 versus the isotype IgG1-injected group.
Mentions: To explore the impact of histone H1 on PCA response in vivo, histone H1 (5 μg/10 μl) was injected intradermally both in the left and right ears. IgE-mediated PCA response induced by DNP-HSA was evaluated by the measurement of evans blue dye in the ears. As shown in Fig 4A, histone H1 without IgE sensitization (left ear) failed to induce PCA response. On the other hand, histone H1 with IgE sensitization (right ear) enhanced PCA response as compared with control group, suggesting the involvement of IgE sensitization for histone H1-mediated type I hyperreactivity. To elucidate anti-allergic mechanism of histone H1-targeted SSV mAb in vivo, SSV mAb or IgG1 isotype control (100 μg/mouse) was intravenously injected into the anti-DNP IgE-treated mice. As shown in Fig 4B, SSV mAb significantly suppressed the extravasation of evans blue compared with vehicle and isotype controls. Taken together, histone H1-targeted SSV mAb suppressed histone H1-mediated mast cell degranulation in vivo.

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