Mechanisms of antigen-induced reactions in skin and lung

Investigators have tried to develop various experimental preparations suitable to study the effects of antigen on skin and airways in order to understand the mechanisms involved in asthma and to develop new methods of diagnosis, prevention and treatment. We have gained considerable experience in studies of specific antigens in inbred dogs with increased levels of serum IgE antibodies to aeroallergens. By using a new method of sensitization, combining an attenuated live virus with a specific and potent antigen, we have developed an experimental preparation that has many features resembling human asthma: High serum levels of IgE antibodies were specifically directed against ragweed antigen. Skin and airway responses to antigen were specific and reproducible. Airway responsiveness to histamine and methacholine aerosols was significantly increased in immunized dogs. Similar to human asthma, ragweed-induced bronchoconstriction in ragweed-sensitized dogs was severe and associated with profound abnormalities in cardiopulmonary function and appeared to be of greater magnitude than usually seen in Ascaris-induced reactions. Ragweed-sensitized dogs had atopic dermatitis, particularly during grass pollen season, confirmed by biopsy and described previously in atopic dogs. Ragweed-sensitized dogs did not have spontaneous wheezing, but usually had diffuse, severe wheezing during induction of anesthesia; cardiac arrhythmias were also common during anesthesia. Ragweed-sensitized dogs appeared to differ from Ascaris-sensitive dogs with respect to skin responsiveness. There was a surprisingly narrow range of skin responsiveness to antigen, whereas Snapper et al. in 1980 reported a wide range of skin responsiveness to Ascaris suum antigen in a group of mongrel dogs. Skin responsiveness to histamine was greater in ragweed-sensitized dogs than in nonimmunized dogs. Similar to human atopic patients, we found frequent late-phase reactions to ragweed antigen. As described below, we showed that antigen-induced mast cell degranulation in skin and airways was associated with inflammation which, in turn, was associated with increased airway responsiveness to pharmacologic agents. The generation of thromboxane by inflammatory cells induced by antigen challenge in ragweed-sensitized dogs appears to play a critical role in altering the response of both airways and skin to pharmacologic agonists.