Alterations of alveolar macrophage function and level of bronchopulmonary protease inhibitors in O,O,S-trimethyl phosphorothioate-induced lung injury.
O,O,S-Trimethyl phosphorothioate (OOS-TMP), an impurity present in widely used organophosphorus insecticides, has been shown to induce pneumotoxicity after oral administration. To date very little is known about the pathogenesis of the injury. Protease-anti-protease imbalance has been proposed as a mechanism of various lung injuries; thus, the effect of OOS-TMP on alpha 1-protease inhibitor capacity, pulmonary alveolar macrophage (PAM) esterases, cytotoxic activity and on specific esterase inhibitors in the bronchopulmonary lavage fluid and serum were measured. OOS-TMP (20 mg/kg) administered orally to rats produced a 27% increase in PAM esterase activity 6 h after treatment. The activity then declined to 63% of control value on day 3 and had not recovered to any significant extent on day 7. The cytotoxic activity of PAM was significantly increased at 6 h and 24 h following treatment. Chymotrypsin inhibitory capacity (CIC) of the lavage fluid was decreased by 45% at 6 h but recovered rapidly and reached control levels by 24 h. Trypsin inhibitory capacity (TIC) of serum was affected to a lesser extent such that no change was detected after 6, 12 or 24 h. These data, early elevation of PAM esterase levels with a concomitant increase in cytotoxic activity and decreased TIC and CIC in bronchopulmonary lavage fluid, support the view that pathogenesis of OOS-TMP produced lung injury could be due to increased protease levels.
D000284:Administration, Oral; D000818:Animals; D002630:Chemotactic Factors; D002860:Chromium Radioisotopes; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D063086:Organothiophosphates / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D011480:Protease Inhibitors / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D007507:Therapeutic Irrigation; D014361:Trypsin Inhibitors / Q000378:metabolism
D002630:Chemotactic Factors; D002860:Chromium Radioisotopes; D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; C019123:O,O,S-trimethyl phosphorothioate; D002918:Chymotrypsin