G. Camussi et al., ROLE OF THE MEMBRANE ATTACK COMPLEX OF COMPLEMENT IN LUNG INJURY MEDIATED BY ANTIBODIES TO ENDOTHELIUM, International archives of allergy and immunology, 102(3), 1993, pp. 216-223
The potential pathogenic role of the membrane attack complex (MAC) of
the complement system was investigated in two models of lung injury me
diated by antibodies to angiotensin-converting enzyme (ACE), an endoth
elial 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 in
dicate that the MAC is required for the pathogenesis of this lung inju
ry. 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 re
duced inflammatory response, and no animals died, implicating a mediat
or function for the MAC in this model as well. These results demonstra
te that MAC is an important mediator of acute pulmonary edema induced
by divalent antibodies to an endothelial antigen. Moreover, the comple
ment system was also, to some extent, involved in the recruitment of i
nflammatory cells leading to the development of interstitial pneumonit
is in the experimental lung injury induced by monovalent anti-ACE Fab
fragments that 'per se' do not activate complement.