Acute pulmonary and renal injury after administration of heterologous anti-lung antibodies in the rat. Characterization of ultrastructural binding sites, basement membrane epitopes, and inflammatory mediation systems.
Male Sprague-Dawley rats developed acute lung and renal injury after administration of heterologous anti-lung antibody. Both organs demonstrated an increase in protein permeability after antibody binding to basement membrane (BM) antigens (lung permeability index 0.342 +/- 0.009 versus control 0.214 +/- 0.011: p less than 0.05. Urinary protein excretion 5.112 +/- 0.899 mg/hour versus control 0.402 +/- 0.008 mg/hour: p less than 0.01). The threshold value for the development of lung injury was 27.2 +/- 4.8 micrograms of antibody globulin/g of tissue (micrograms/gm). Immunoblot analysis probing with the anti-lung antibody revealed at least one common antigenic determinant (82 to 84 kilodaltons) bound within collagenase-solubilized pulmonary and glomerular BMs. Increasing doses of antibody produced hemorrhagic pneumonitis and diffuse alveolar damage. Immunofluorescence microscopy confirmed linear alveolar and glomerular BM antibody binding. Immunogold electron microscopy allowed precise identification, in intense linear patterns, of BM binding sites within lung and glomeruli. Functional lung injury was prevented by either leukocyte-depletion or complement-depletion (lung permeability index antibody-treated, complement-depleted 0.235 +/- 0.034: both p greater than 0.05 compared with controls). Injury mediation in this acute humoral model of lung damage is both complement- and leukocyte-dependent, as previously described for the renal component of heterologous anti-glomerular BM antibody-induced inflammatory disease.
Boyce
N W
NW
Department of Medicine, Monash University, Prince Henry's Hospital, Melbourne, Australia.
Fernando
N S
NS
Neale
T J
TJ
Holdsworth
S R
SR
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001485:Basement Membrane / Q000276:immunology / Q000648:ultrastructure; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000032:analysis*; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D007249:Inflammation; D007668:Kidney / Q000473:pathology* / Q000648:ultrastructure; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D016253:Microscopy, Immunoelectron; D051381:Rats; D011919:Rats, Inbred Strains; D013861:Thiocyanates
D000906:Antibodies; D000939:Epitopes; D005452:Fluoresceins; D005456:Fluorescent Dyes; D013861:Thiocyanates; D016650:Fluorescein-5-isothiocyanate