OXIDANTS FROM NEUTROPHIL MYELOPEROXIDASE DO NOT ENHANCE ELASTASE-INDUCED EMPHYSEMA IN THE HAMSTER

Alpha-1-protease inhibitor is susceptible to oxidative impairment by t he neutrophil myeloperoxidase (MPO) system. The purpose of this study was to assess the effect of the MPO oxidant system on elastase-induced emphysema in the hamster. Intratracheal instillation of 200 mug of hu man neutrophil elastase (HNE) induced a significant secretory cell met aplasia (SCM) and airspace enlargement [23% increase in mean linear in tercept (MLI) as compared with control values]. Instillation of MPO sy stem components [0.6 international units (U) of MPO, 5.5 U of glucose oxidase and glucose (0.02 M)] along with 200 mug HNE failed to enhance the severity of the SCM or emphysema induced by HNE alone. A second e xperiment was carried out using 50 mug of porcine pancreatic elastase (PPE) to induce emphysema. PPE produced a significant 45% increase in MLI, but the MPO system combined with PPE failed to enhance the emphys ema induced by PPE alone. The MPO system alone had no measurable effec t on airspace size or SCM. In vitro studies showed that PPE was partia lly inactivated by the MPO system; a 56% loss of elastolytic activity occurred during a 6-min incubation of PPE with the MPO system. This ma y explain why the MPO system did not exacerbate PPE-induced injury, bu t it does not explain the lack of enhancement for HNE. A 6-minute incu bation of HNE with the MPO system resulted in a nonsignificant 10% dec rease of elastolytic activity. The failure to demonstrate enhancement of HNE-induced emphysema in the hamster by MPO system-generated oxidan ts instilled intratracheally does not exclude the possibility of such an enhancement in microenvironments of the lungs or under conditions i n which hemorrhage is minimized.