In vitro and in vivo effects of chloramine T on rat serum elastase inhibitor.

Recent studies have shown that oxidizing agents may block the elastase inhibitory activity of alpha 1-antiproteinase in humans and some animal species. It has been postulated that this protein plays a critical role in modulating the activity of the neutral proteinase, i.e. elastase, in the lung; its inactivation has been implicated in the destruction of lung tissue seen in emphysema. In this work, we have studied the inactivation in vitro of rat serum elastase inhibitor by chloramine T (CT) and whether the in vivo use of the same oxidizing agent in the development of a functional model of alpha 1-antiproteinase deficiency in the rat is feasible. Although serum alpha 1-antiproteinase is readily inactivated in vitro by CT, it was observed, in vivo, that serum elastase inhibitory capacity was reduced to about 28-35% of initial levels 1-3 h after CT injection, and returned to control values within 9 h. Therefore, the in vivo study demonstrated that in the rat a functional model of alpha 1-antiproteinase deficiency cannot be achieved by inactivation of the protein molecule with CT. The relatively short half-life (1.45 h) of the serum elastase inhibitor found in normal rats is consistent with a rapid synthesis of the protein molecule, which might contribute to the fast recovery of the elastase inhibitory capacity observed in experimental animals after CT administration.