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局部皮肤用过敏原特异性 IgG1 单克隆抗体的 Fab 片段治疗可抑制小鼠变应性特应性皮炎样皮肤损伤。

Topical skin treatment with Fab fragments of an allergen-specific IgG1 monoclonal antibody suppresses allergen-induced atopic dermatitis-like skin lesions in mice.

机构信息

Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada, Kobe 658-8558, Japan; Interdisciplinary Graduate School of Nutraceutical and Functional Food Research and Development Center, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand.

Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada, Kobe 658-8558, Japan.

出版信息

Eur J Pharmacol. 2016 May 15;779:131-7. doi: 10.1016/j.ejphar.2016.03.020. Epub 2016 Mar 9.

DOI:10.1016/j.ejphar.2016.03.020
PMID:26970183
Abstract

Fab fragments (Fabs), which lack effector functions due to the absence of the Fc portion, maintain the ability to bind to specific allergens. In the present study, we examined whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) were able to regulate allergen-induced atopic dermatitis-like skin lesions in mice. BALB/c mice passively sensitized with ovalbumin (OVA)-specific IgE mAb were repeatedly challenged with OVA applied to the skin after sodium dodecyl sulfate treatment. Fabs prepared by the digestion of anti-OVA IgG1 mAb (O1-10) with papain were applied to the skin 30min before the OVA challenges followed by measurement of clinical symptoms including erythema/hemorrhage, edema, scarring/dryness, and excoriation/erosion of the skin. Treatment with O1-10 Fabs, but not intact O1-10, showed inhibition of clinical symptoms (P<0.01) induced by the repeated OVA challenges in the sensitized mice; O1-10 Fabs suppressed histological changes such as epidermal hyperplasia (P<0.01) and the accumulation of mast cells (P<0.01) and neutrophils (P<0.01). Furthermore, treatment with O1-10 Fabs inhibited the increase in levels of IL-13 (P<0.01) and IL-17A production (P<0.05) in the lymph nodes of the sensitized mice. Additionally, the increased level of OVA in serum following the repeated OVA challenges in the sensitized mice was reduced by the treatment (P<0.05). These results suggest that topical application of pathogenic allergen-specific IgG1 mAb Fabs to the skin of mice is effective in suppressing allergen-induced atopic dermatitis-like skin lesions, suggesting that allergen-specific mAb Fabs could be used as a tool to regulate allergen-induced atopic dermatitis.

摘要

Fab 片段(Fabs)由于缺乏 Fc 部分而丧失效应功能,但仍保持与特定过敏原结合的能力。在本研究中,我们研究了过敏原特异性 IgG1 单克隆抗体(mAb)的 Fab 片段是否能够调节小鼠的变应性特应性皮炎样皮肤损伤。用卵清蛋白(OVA)特异性 IgE mAb 被动致敏的 BALB/c 小鼠在用十二烷基硫酸钠处理后,皮肤反复接受 OVA 挑战。用木瓜蛋白酶消化抗 OVA IgG1 mAb(O1-10)制备 Fab 片段,在 OVA 挑战前 30min 应用于皮肤,然后测量包括红斑/出血、水肿、瘢痕/干燥和皮肤抓挠/糜烂在内的临床症状。用 O1-10 Fab 片段治疗,但不用完整的 O1-10 治疗,可抑制致敏小鼠中重复 OVA 挑战引起的临床症状(P<0.01);O1-10 Fab 片段抑制表皮过度增生(P<0.01)、肥大细胞(P<0.01)和中性粒细胞(P<0.01)积聚等组织学变化。此外,O1-10 Fab 片段治疗抑制了致敏小鼠淋巴结中白细胞介素-13(IL-13)(P<0.01)和白细胞介素-17A 产生(P<0.05)的增加。此外,用 O1-10 Fab 片段治疗可降低致敏小鼠在重复 OVA 挑战后血清中 OVA 水平的增加(P<0.05)。这些结果表明,将致病过敏原特异性 IgG1 mAb Fab 片段局部应用于小鼠皮肤可有效抑制过敏原诱导的特应性皮炎样皮肤损伤,提示过敏原特异性 mAb Fab 片段可用作调节过敏原诱导的特应性皮炎的工具。

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