Role of the membrane attack complex of complement in lung injury mediated by antibodies to endothelium.
The potential pathogenic role of the membrane attack complex (MAC) of the complement system was investigated in two models of lung injury mediated by antibodies to angiotensin-converting enzyme (ACE), an endothelial cell enzyme. In the first model, acute and fatal lung edema was induced in rabbits by intravenous administration of divalent anti-ACE antibodies. These animals died acutely. C6-deficient rabbits tolerated anti-ACE antibodies without apparent ill effects. On the other hand, C6-deficient rabbits reconstituted with C6 and then receiving anti-ACE antibodies developed acute pulmonary edema and died. These results indicate that the MAC is required for the pathogenesis of this lung injury. In the second model, intravenous administration of monovalent anti-ACE Fab fragments over 4 consecutive days induced fatal interstitial pneumonitis in normal rabbits. For C6-deficient rabbits there was a reduced inflammatory response, and no animals died, implicating a mediator function for the MAC in this model as well. These results demonstrate that MAC is an important mediator of acute pulmonary edema induced by divalent antibodies to an endothelial antigen. Moreover, the complement system was also, to some extent, involved in the recruitment of inflammatory cells leading to the development of interstitial pneumonitis in the experimental lung injury induced by monovalent anti-ACE Fab fragments that 'per se' do not activate complement.
Camussi
G
G
Department of Pathology, School of Medicine, State University of New York at Buffalo.
Biesecker
G
G
Caldwell
P R
PR
Biancone
L
L
Andres
G
G
Brentjens
J R
JR
D000208:Acute Disease; D000818:Animals; D002196:Capillaries / Q000276:immunology; D002199:Capillary Permeability; D003183:Complement C6 / Q000172:deficiency; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D008854:Microscopy, Electron; D007703:Peptidyl-Dipeptidase A / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology; D011654:Pulmonary Edema / Q000276:immunology*; D011817:Rabbits
D003183:Complement C6; D015938:Complement Membrane Attack Complex; D007703:Peptidyl-Dipeptidase A