MODULATION OF THE LATE ASTHMATIC RESPONSE BY ANTIGEN-SPECIFIC IMMUNOGLOBULIN-G IN AN ANIMAL-MODEL

Abstract

The late asthmatic response (LAR) occurs 4-12 h after antigenic challenge and has been related to the severity of asthma. In addition, improvement of asthmatic symptoms after immunotherapy has also been related to loss of the LAR. Because the LAR seems to be a critical component of asthma, an animal model of the LAR was employed to study its immunopathogenesis concentrating on the role of antigen-specific rabbit homocytotropic (IgE) and heterocytotropic (IgG) antibodies to Alternaria tenuis. Serum samples from rabbits previously immunized with Alternaria extract were infused into age-matched previously nonimmunized recipients. Groups of recipients were categorized according to the immune status of the transfused serum: E-only, E/G, subdivided into E/low G (1:256 to 1:512) and E/high G (1:2048), G (serum heat-treated to minimize IgE), and Control (transfused with serum from nonimmunized rabbits). Subsequently, pulmonary function was measured before and for 6 h after challenge with aerosolized A. tenuis by recording pulmonary resistance, functional residual capacity by helium dilution, specific conductance, and dynamic compliance. The E-only recipients showed an immediate asthmatic response followed by a marked LAR comparable in magnitude to actively immunized animals. The E/G recipients showed blunting of the LAR in a dose-dependent fashion, with increasing titers of IgG antibody. The G recipients showed no immediate or late responses. Immunofluorescent studies in selected animals from each group failed to show any granular deposition of Ig or C3 in either the airways or blood vessels of the lung. Antigen-specific IgG in the passively transferred LAR is evidently protective in a dose-dependent manner in this model.