Role of polyclonal cell activation in the initiation of immune complex-mediated pulmonary injury following antigen inhalation.
The lung, by virtue of its anatomic situation, provides environmental antigens with unique access to host lymphoid tissues. In order to better understand the biologic consequences of antigen inhalation, we developed in animal model in which soluble proteins are administered in aerosol form to rabbits. By labeling these proteins with fluorochrome dyes or radioactive isotopes, the uptake, distribution, and fate of such proteins can be demonstrated both morphologically and quantitatively. Prompt host-antibody responses can be demonstrated to inhaled antigen, but not to comparable amounts of ingested antigen. Repeated administrations of antigen aerosol to immune animals produced little injury; in contrast, administration of aerosols containing phytohemagglutinin or cancanavalin A (Con A), plant lectins which activate leucocytes in a polyclonal fashion, induced a diffuse interstitial pneumonitis. When immune animals inhaled antigen plus Con A, devastating pulmonary necrosis was induced, in association with localized deposits of immune complexes containing antigen, antibody and complement. Such necrotic injury healed by scarring within 4 weeks. The necrotizing injury could be prevented by either decomplementation with cobra venom factor, or through inhibition of leucocyte responsiveness to Con A by administration of cholera toxin, a cAMP agonist. These studies indicate that antigen inhalation may serve as an important means of establishing "natural" immunity to environmental agents, but also may lead to severe pulmonary injury and fibrosis where the agents inhaled act not only as antigens but as polyclonal leucocyte activators as well.
D000336:Aerosols; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001183:Arthus Reaction / Q000276:immunology; D002772:Cholera Toxin / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007105:Immune Complex Diseases / Q000209:etiology*; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D011817:Rabbits; D012130:Respiratory Hypersensitivity / Q000209:etiology*; D012710:Serum Albumin, Bovine / Q000276:immunology; D012882:Skin Tests
D000336:Aerosols; D000941:Antigens; D003208:Concanavalin A; D012710:Serum Albumin, Bovine; D002772:Cholera Toxin; D000242:Cyclic AMP; D006152:Cyclic GMP