Alterations of alveolar macrophage function and level of bronchopulmonary protease inhibitors in O,O,S-trimethyl phosphorothioate-induced lung injury.
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| Abstract |
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.
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| Authors | T Imamura, I K Thomas |
| Journal | Toxicology (Toxicology) Vol. 37 Issue 1-2 Pg. 79-89 (Oct 1985) ISSN: 0300-483X [Print] Ireland |
| PMID | 4060171 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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