Leukocyte involvement in the pathogenesis of pulmonary injury in experimental Goodpasture's syndrome.
To investigate the role of leukocytes in the pathogenesis of pulmonary injury after antibody deposition on the alveolar basement membrane, we have induced experimental Goodpasture's syndrome in the rat using passive accelerated anti-glomerular basement membrane (GBM) disease. Animals were immunized with normal rabbit IgG and given either rabbit anti-rat GBM serum or normal rabbit serum (control) 5 days later. In this model, leukocytic infiltration, severe hemorrhage, and granulomatous-like lesions developed in the lung, while a rapidly progressive glomerulonephritis was evident in the kidney. Within 30 minutes of injection of anti-GBM serum, strong linear deposition of antibody on both glomerular and alveolar basement membranes was evident. In the lung, a transient influx of polymorphonuclear cells during the first 12 hours was closely followed by macrophage infiltration, with T cell infiltration not evident until day 3. Pulmonary hemorrhage correlated with ED1+ macrophage infiltration (p less than 0.001), but not with OX-19+ T cell accumulation. Many activated mononuclear cells were found in the lung infiltrate from day 14 onward and were associated with areas of tissue damage. This study demonstrates the feasibility of using passive accelerated anti-GBM disease as a model of Goodpasture's syndrome, and suggests that inflammatory macrophages are the major cellular participants in progressive pulmonary injury after antibody deposition.
Lan
H Y
HY
Department of Nephrology, Monash Medical Centre, Prince Henry's Hospital, Melbourne, Australia.
Paterson
D J
DJ
Hutchinson
P
P
Atkins
R C
RC
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000473:pathology*; D002465:Cell Movement; D005434:Flow Cytometry; D006470:Hemorrhage / Q000209:etiology / Q000473:pathology; D007668:Kidney / Q000473:pathology; D007962:Leukocytes / Q000502:physiology*; D008168:Lung / Q000473:pathology*; D008171:Lung Diseases / Q000209:etiology / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000502:physiology