Matsuoka Daiko, Mizutani Nobuaki, Sae-Wong Chutha, Yoshino Shin
Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada, Kobe 658-8558, Japan.
Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada, Kobe 658-8558, Japan.
Immunol Lett. 2014 Sep;161(1):149-56. doi: 10.1016/j.imlet.2014.06.005. Epub 2014 Jun 19.
Fab fragments (Fabs) have the ability to bind to specific antigens but lack the Fc portion for binding to receptors on immune and inflammatory cells that play a critical role in allergic diseases. In the present study, we investigated whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) inhibited allergic rhinitis in mice. BALB/c mice sensitized by intraperitoneal injections of ovalbumin (OVA) plus alum on days 0 and 14 were intranasally challenged with OVA on days 28-30, and 35. Fabs prepared by the digestion of an anti-OVA IgG1 mAb (O1-10) with papain were also intranasally administered 15min before each OVA challenge. The results showed that treatment with O1-10 Fabs significantly suppressed the sneezing frequency, associated with decrease of OVA-specific IgE in the serum and infiltration by mast cells in the nasal mucosa seen following the fourth antigenic challenge; additionally, the level of mouse mast cell protease-1, a marker of mast cell activation, in serum was decreased. Furthermore, infiltration of eosinophils and goblet cell hyperplasia in the nasal mucosa at the fourth challenge were inhibited by treatment with O1-10 Fabs. In conclusion, these results suggest that intranasal exposure to Fabs of a pathogenic antigen-specific IgG1 mAb may be effective in regulating allergic rhinitis through allergen capture by Fabs in the nasal mucosa before the interaction of the intact antibody and allergen.
Fab片段(Fabs)具有结合特定抗原的能力,但缺乏可与免疫和炎症细胞上的受体结合的Fc部分,而这些受体在过敏性疾病中起着关键作用。在本研究中,我们调查了过敏原特异性IgG1单克隆抗体(mAb)的Fabs是否能抑制小鼠的过敏性鼻炎。在第0天和第14天通过腹腔注射卵清蛋白(OVA)加明矾致敏的BALB/c小鼠,在第28 - 30天和第35天用OVA进行鼻内激发。在用木瓜蛋白酶消化抗OVA IgG1 mAb(O1 - 10)制备的Fabs也在每次OVA激发前15分钟进行鼻内给药。结果显示,用O1 - 10 Fabs治疗可显著抑制打喷嚏频率,这与第四次抗原激发后血清中OVA特异性IgE的降低以及鼻黏膜中肥大细胞浸润的减少有关;此外,血清中作为肥大细胞活化标志物的小鼠肥大细胞蛋白酶-1水平降低。此外,用O1 - 10 Fabs治疗可抑制第四次激发时鼻黏膜中嗜酸性粒细胞的浸润和杯状细胞增生。总之,这些结果表明,在完整抗体与过敏原相互作用之前,通过鼻黏膜中Fabs捕获过敏原,鼻内暴露于致病性抗原特异性IgG1 mAb的Fabs可能对调节过敏性鼻炎有效。