Lung injury induced by antibody fragments to angiotensin-converting enzyme.
Rabbits given goat anti-rabbit angiotensin-converting enzyme antibodies or derived antibody fragments develop rapidly fatal pulmonary edema. Endothelial cell injury is manifested by bleb formation and the disintegration of cell membranes. Platelets are found along the injured endothelium and leukocytes block capillary lumens. The pathologic features are similar when immune IgG, F(ab')2, or Fab are given. In vitro studies of complement activation show that solubilized, purified angiotensin-converting enzyme alone activates C1, with consumption of C4 and C3. Addition of immune IgG plus converting enzyme enhances this activation. F(ab')2 plus enzyme enhances only C3 consumption, while Fab with enzyme produces no additional complement utilization. Thus, while complement activation may be involved in the pathogenesis of injury induced by IgG or F(ab')2, the mechanism of Fab-induced endothelial injury remains unclear.
D000818:Animals; D002462:Cell Membrane / Q000276:immunology; D003167:Complement Activation; D003172:Complement C1 / Q000276:immunology; D003176:Complement C3 / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D006041:Goats / Q000276:immunology; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007703:Peptidyl-Dipeptidase A / Q000276:immunology*; D011654:Pulmonary Edema / Q000209:etiology / Q000276:immunology*; D011817:Rabbits
D003172:Complement C1; D003176:Complement C3; D003181:Complement C4; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007703:Peptidyl-Dipeptidase A