Antigen-specific immunoglobulin-A prevents increased airway responsiveness and lung eosinophilia after airway challenge in sensitized mice.
Aeroallergens such as Amb a I from short ragweed are important in the development of allergic airway disease. We tested the ability of a human monoclonal immunoglobulin-A (IgA) antibody specific for Amb a I (A-IgA) to modulate airway responsiveness and lung eosinophilia after airway challenge with nebulized Amb a I or ragweed extract in mice sensitized to Amb a I or ragweed extract, respectively. A-IgA or nonspecific IgA (C-IgA) were given intranasally up to 8 h before each challenge. Allergen challenge resulted in increases in airway responsiveness, in numbers of lung eosinophils, and in Amb a I-specific IgE levels. These were prevented by pretreatment with A-IgA but not with C-IgA. Decreases in IFN-gamma and increases in IL-4 and IL-5 production following challenge with Amb a I were also reduced by A-IgA treatment. In contrast, increases in total IgE and total IgG and in numbers of lung neutrophils after challenge were not significantly affected by A-IgA, which additionally induced increased levels of Amb a I-specific IgG2a antibodies. In mice sensitized and challenged with ovalbumin (OVA), A-IgA did not affect airway responsiveness, lung eosinophilia, cytokine production, or immunoglobulin levels. These data indicate that allergen-specific IgA can prevent airway hyperresponsiveness and reduce eosinophil influx into the lungs following allergen challenge via the airways in sensitized mice, and these effects are allergen-specific. Neutralization of allergen may contribute to the effects of IgA, but the induction of allergen-specific IgG2a in A-IgA-treated mice suggests an immunomodulatory action for A-IgA.
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA.
J
J
Schwarze
G
G
Cieslewicz
A
A
Joetham
L K
LK
Sun
W N
WN
Sun
T W
TW
Chang
E
E
Hamelmann
E W
EW
Gelfand
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001985:Bronchial Provocation Tests; D016207:Cytokines; D004195:Disease Models, Animal; D004802:Eosinophilia; D005260:Female; D007070:Immunoglobulin A / Q000502:physiology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007070:Immunoglobulin A