Experimental anti-alveolar basement membrane antibody-mediated pneumonitis. I. The role of increased permeability of the alveolar capillary wall induced by oxygen.
Attempts to produce in animals lung lesions mediated by anti-alveolar basement membrane (ABM) antibodies have thus far been inconclusive. The aim of the present study was to test the hypothesis that increased permeability of the endothelial cell lining is needed before circulating antibodies can gain access and bind to ABM. A goat antiserum was prepared against purified rabbit ABM. After i.v. injection of the gamma-globulin fraction into rabbits, goat IgG was detected in glomerular basement membrane but not in ABM. However, 17 of 19 rabbits injected with anti-ABM antibody after exposure for 62 to 66 hr to 100% oxygen had a diffuse linear binding of goat IgG in ABM and died with pulmonary edema and hemorrhagic pneumonitis. By the paired label isotope technique, uptake of anti-ABM antibodies in lung far exceeded that in kidney. Semiquantitative histologic studies indicated that the lesions in the lung of these rabbits were more severe then those found in rabbits exposed to 100% oxygen and injected with normal goat serum gamma-globulin. None of the latter animals died with pulmonary edema; none was found to have binding of goat IgG in the lung. The results indicate that under normal physiologic conditions the endothelium is a barrier that prevents binding of IgG antibodies to ABM. The increased permeability induced by oxygen in the alveolar capillary wall is a nonimmunologic factor allowing the development of a reproducible model of severe anti-ABM antibody-mediated pneumonitis.
D000818:Animals; D000906:Antibodies; D001485:Basement Membrane / Q000276:immunology; D002199:Capillary Permeability; D005260:Female; D006041:Goats; D007668:Kidney / Q000276:immunology; D008099:Liver / Q000276:immunology; D010100:Oxygen / Q000494:pharmacology*; D011014:Pneumonia / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology*; D011654:Pulmonary Edema / Q000276:immunology / Q000401:mortality; D011817:Rabbits; D013154:Spleen / Q000276:immunology; D005719:gamma-Globulins / Q000276:immunology
D000906:Antibodies; D005719:gamma-Globulins; D010100:Oxygen