Pathogenesis of an experimental model of Goodpasture's hemorrhagic pneumonitis.
The mechanisms that allow circulating basement membrane antibodies (Ab) to interact with the alveolar basement membrane (ABM) inducing Goodpasture's hemorrhagic pneumonitis are unknown. In laboratory animals the ABM is inaccessible to phlogogenic amounts of ABM Ab unless the permeability of the unfenestrated alveolar endothelium is increased. This study was designed to test the hypothesis that in the mouse polypeptide mediators, generated by activated lymphoid cells or cells infected by viruses, contribute to the pathogenesis of passive Goodpasture's hemorrhagic pneumonitis. In naive mice that received rabbit ABM Ab, these bound to the glomerular basement membrane but not to the ABM and their lungs were normal. In the lungs of mice injected with human recombinant IL-2 and IFN-alpha specific binding of ABM IgG, C3, and fibrinogen to the ABM, diffuse and severe erythrocyte extravasation, and accumulation of mononuclear and polymorphonuclear leukocytes were constantly observed. ABM Ab and IL-2 or ABM Ab and IFN-alpha did not produce comparable effects. Mice injected only with IL-2 and IFN-alpha had enlarged, edematous lungs without pulmonary hemorrhages. The results show that the synergism of IL-2 and IFN-alpha convert the lung into a preferential target for AMB Ab, suggesting that cytokines may have a role in the pathogenesis of human Goodpasture's pneumonitis.
Queluz
T H
TH
Department of Microbiology, State University of New York, Buffalo 14214.
Pawlowski
I
I
Brunda
M J
MJ
Brentjens
J R
JR
Vladutiu
A O
AO
Andres
G
G
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D000911:Antibodies, Monoclonal; D001485:Basement Membrane / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D007074:Immunoglobulin G; D007370:Interferon Type I / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins