TOBACCO SMOKE-INDUCED LUNG EMPHYSEMA IN GUINEA-PIGS IS ASSOCIATED WITH INCREASED INTERSTITIAL COLLAGENASE

We examined the expression of interstitial collagenase and its enzymat ic activity in lung damage induced by tobacco smoke. Guinea pigs were exposed to the smoke of 20 cigarettes per day from 1-8 wk. Age-matched guinea pigs were used as controls. At 6 and 8 wk of smoke exposure, l ungs exhibited interstitial and peribronchiolar inflammation and moder ate emphysematous changes. In situ hybridization of injured lungs reve aled patchy expression of collagenase mRNA mainly in macrophages but a lso in alveolar epithelial and interstitial cells. Immunoreactive prot ein was detected in alveolar macrophages and in the alveolar walls and interstitium. Collagenolytic activity increased beginning in the 4th wk of exposure (0.7 +/- 0.43 mu g collagen degraded/mg collagen incuba ted relative to 0.23 +/- 0.14 in controls; P < 0.05). At 6 and 8 wk, v alues were 0.85 +/- 0.34 and 0.98 +/- 0.33 compared with 0.25 +/- 0.11 and 0.26 +/- 13 in controls (P < 0.005 and 0.001). Collagen concentra tion decreased from 50.7 +/- 8.5 mg/g dry wt in control lungs to 40.2 +/- 5.0 and 42.9 +/- 6.0 at 6 and 8 wk of exposure, respectively (P < 0.05). These results strongly suggest that increased interstitial coll agen degradation plays a role in the development of lung emphysema.