BIOCHEMICAL-ALTERATIONS IN RAT LUNG LAVAGE FLUID FOLLOWING ACUTE SULFUR MUSTARD INHALATION .2. INCREASES IN PROTEOLYTIC ACTIVITY

Inhalation exposure of rats to sulfur mustard (HD) followed by assay o f lung lavage fluid with Chromozym TH (thrombin-like) and TRY (trypsin -like) serine protease substrates revealed a time-dependent increase i n proteolytic activity. HD (0.35 mg) in absolute ethanol (100 mu l) or ethanol alone (control) was placed in a glass vapor generator at 37 d egrees C, and test rats were subjected to inhalation exposure for 50 m in. Increased proteolysis of the TH substrate (2.6 times control level s) was seen at 4 h after HD exposure, and enhanced proteolysis of both TH and TRY substrates, 13.1 and 2.6 times control levels, respectivel y, was observed at 24 h. HD inhalation exposure causes lung pathology that includes multifocal petechial hemorrhages, epithelial necrosis, a nd separation at the mucosal-submucosal interface beginning at 6 h pos texposure, with atelectasis and edema beginning at 12-18 h, and these pathological changes become more pronounced at 24 h post HD exposure ( Anderson et al., 1996). The increased proteolytic activity at 4 and 24 h post HD exposure in rat lung lavage fluid is coincident with the ti me course of onset and development of tissue pathology in lung followi ng HD exposure. HD-increased proteolysis may provide a biochemical mar ker for HD-induced pathology that might facilitate identification of m echanisms of HD action and of medical countermeasures to HD.