title: Allergen-specific regulation of allergic rhinitis in mice by intranasal exposure to IgG1 monoclonal antibody Fab fragments against pathogenic allergen.
abstract: 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.
authors: Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada, Kobe 658-8558, Japan.
authors: Daiko
authors: D
authors: Matsuoka
authors: Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada, Kobe 658-8558, Japan. Electronic address: mizutani@kobepharma-u.ac.jp.
authors: Nobuaki
authors: N
authors: Mizutani
authors: Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada, Kobe 658-8558, Japan.
authors: Chutha
authors: C
authors: Sae-Wong
authors: Department of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada, Kobe 658-8558, Japan.
authors: Shin
authors: S
authors: Yoshino
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D056747:Immunomodulation; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010047:Ovalbumin / Q000009:adverse effects / Q000276:immunology; D065631:Rhinitis, Allergic / Q000276:immunology*
chemical_list: D000485:Allergens; D018932:Chemokine CCL2; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Allergic rhinitis; Fab fragment; Monoclonal antibody; Sneeze