title: Intratracheal exposure to Fab fragments of an allergen-specific monoclonal antibody regulates asthmatic responses in mice.
abstract: Fab fragments (Fabs) maintain the ability to bind to specific antigens but lack effector functions due to the absence of the Fc portion. In the present study, we tested whether Fabs of an allergen-specific monoclonal antibody (mAb) were able to regulate asthmatic responses in mice. Asthmatic responses were induced in BALB/c mice by passive sensitization with anti-ovalbumin (OVA) polyclonal antibodies (pAbs) (day 0) and by active sensitization with OVA (days 0 and 14), followed by intratracheal (i.t.) challenge with OVA on day 1 and days 28, 29, 30 and 35. Fabs prepared by the digestion of an anti-OVA IgG1 (O1-10) mAb with papain were i.t. administered only once 30 min before antigenic challenge on day 1 or day 35. The results showed that i.t. administration of O1-10 Fabs with OVA markedly suppressed the early and/or late phases of asthmatic responses caused by passive and active sensitization. Similar results were obtained when Fabs of anti-OVA IgG2b mAb (O2B-3) were i.t. administered. In contrast, neither i.t. injection of intact 01-10/O2B-3 nor systemic injection of O1-10 Fabs suppressed the asthmatic responses. In vitro studies revealed that the capture of OVA by O1-10 Fabs prevented the subsequent binding of intact anti-OVA pAbs to the captured OVA. These results suggest that asthmatic responses may be down-regulated by the i.t. exposure to Fabs of an allergen-specific mAb via a mechanism involving the capture of allergen by Fabs in the respiratory tract before the interaction of intact antibody and allergen essential for the induction of asthmatic responses.
authors.affiliation: Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Yoshino
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Mizutani
authors.forename: Daiko
authors.initials: D
authors.lastname: Matsuoka
authors.forename: Chutha
authors.initials: C
authors.lastname: Sae-Wong
mesh_terms: D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000276:immunology*; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D013997:Time Factors
chemical_list: D000485:Allergens; D018926:Anti-Allergic Agents; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010047:Ovalbumin
keywords: Fab; asthma; intratracheal exposure; monoclonal antibody