Lung injury mediated by antibodies to endothelium. III. Effect of chlorpromazine in rabbits.
In rabbits intravenous administration of antibodies to lung angiotensin converting enzyme (ACE) results in a rapid redistribution of ACE on the plasma membrane of pulmonary endothelium with fixation of complement and development of fatal pulmonary edema. In survivors given daily injections of antibodies, ACE disappears from the lung ("antigenic modulation") and the rabbits become resistant to further immune injury. To test the hypothesis that these events depend on a functionally intact mechanism of cell activation, rabbits received, in addition to anti-ACE antibodies, chlorpromazine, a drug that inhibits calmodulin and protein kinase C and decreases plasma membrane fluidity. Initially, chlorpromazine inhibited antigen redistribution, fixation of complement, and development of pulmonary edema. In rabbits maintained on chlorpromazine and receiving daily anti-ACE antibodies this effect became attenuated and the rabbits eventually developed ACE redistribution, complement fixation, and pulmonary edema. We conclude that chlorpromazine temporarily inhibits antigenic modulation in vivo, presumably through its action on calcium-mediated antibody-cell surface antigen interaction.
Camussi
G
G
Department of Pathology, School of Medicine, State University of New York, Buffalo 14214.
Brentjens
J R
JR
Andres
G
G
Caldwell
P R
PR
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D002746:Chlorpromazine / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects / Q000276:immunology; D005260:Female; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D007703:Peptidyl-Dipeptidase A / Q000276:immunology; D011654:Pulmonary Edema / Q000276:immunology; D011817:Rabbits
D000906:Antibodies; D000954:Antigens, Surface; D007703:Peptidyl-Dipeptidase A; D002746:Chlorpromazine