The effect of alphanapthylthiourea (ANTU)-induced acute injury on lung binding of antibody to angiotensin converting enzyme (ACE).
The effects of ANTU-induced acute pulmonary capillary injury on lung and serum ACE functional activity and the specific accumulation of radio-labelled anti-ACE in lung were explored. Rats were injected either with ANTU or the solvent and sacrificed at various intervals up to one week after injection. All ANTU-injected animals developed pulmonary edema and bilateral pleural effusions which resolved by the one week time point. At no time was there any significant change in serum ACE levels. The specific activity of total lung ACE however rose from 11.0 +/- .95 (mean +/- SEM) to 18.4 +/- 1.1 by two hours after ANTU; by 24 hours, however, solubilized lung ACE had fallen significantly to 6.9 +/- .79 (p less than .01). Total lung ACE had returned to control values by one week. In parallel groups of animals the accumulation of 125I-labelled anti-ACE (AA) or normal sheep immunoglobulin (NSG) was compared in control and ANTU-treated rats. The ratio of the radioactivity in the lungs of AA--injected animals to that in NSG--injected animals fell significantly after ANTU administration (5.0 +/- .88 to 1.2 +/- .28 at 2 hours) suggesting that immunoreactive ACE had fallen despite an increase in ACE functional activity. The decreased binding of AA at the early time points perhaps reflects internalization of endothelial cell ACE in response to injury and an inability of the antibody to interact with the enzyme. The reduction in binding at 24 hours (1.38 +/- .47) correlates with a reduction in total lung ACE. ANTI-ACE may be a useful reagent for quantitating endothelial cell damage following lung injury.
D000818:Animals; D000906:Antibodies; D000936:Antigen-Antibody Complex; D007136:Immunoglobulins; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D013890:Thiourea / Q000031:analogs & derivatives* / Q000633:toxicity
D000906:Antibodies; D000936:Antigen-Antibody Complex; D007136:Immunoglobulins; D007703:Peptidyl-Dipeptidase A; D013890:Thiourea; C005277:alpha-naphthyl thiourea