We seek support for our studies of an inbred colony of allergic dogs, now in its fifth generation. These dogs are given live viral vaccines at the time of immunization with ragweed pollen antigen in infancy; within weeks they develop specific IgE antibodies. Upon maturity, they experience antigen-induced immediate and late-phase reactions in airways, skin and nose, comparable to allergic human patients. These unique dogs present an extraordinary opportunity to study the pathogenesis of allergic reactions by immunopharmacologic, biochemical, physiologic, and anatomic methods.
Specific aims are to assess the anatomic and biochemical responses to immunologic and nonimmunologic stimuli on atypical and typical mast cells and on circulating and resident inflammatory cells (granulocytes, platelets, mononuclear cells) in skin and airways; and assess the contribution of these cells to early- and late-phase inflammatory responses and to increased physiologic responses to histamine and acetylcholine in skin and airways, respectively. We intend to define the anatomic and functional characteristics of cultured dog airway mast cells in vitro and compare them to subsets of mast cells in dog skin in vivo (using serial skin biopsies and surface chambers to collect secreted mediators) in response to nonimmunologic and immunologic stimuli. We shall examine the role of different types of mast cells in skin and airways in triggering inflammatory responses and the roles of neutrophils and eosinophils in production of increased skin and airway responsiveness following exposure to antigen. Hydroxyurea and poly- and monoclonal antisera to neutrophils and eosinophils will be used to deplete such cells so that responsiveness can be compared in presence or absence of these cells. Drugs, humoral agents, and transfused IgG antibodies will be given to try to modulate these responses in skin and airways. Hopefully, these results will suggest new approaches that can be applied in future studies to prevent or treat diseases in human allergic patients.
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