Alpha-1-protease inhibitor is susceptible to oxidative impairment by the 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 μg of human neutrophil elastase (HNE) induced a significant secretory cell metaplasia (SCM) and airspace enlargement [23% increase in mean linear intercept (MLI) as compared with control values]. Instillation of MPO system components [0.6 international units (U) of MPO, 5.5 U of glucose oxidase and glucose (0.02 M)] along with 200 μg HNE failed to enhance the severity of the SCM or emphysema induced by HNE alone. A second experiment was carried out using 50 μg 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 emphysema induced by PPE alone. The MPO system alone had no measurable effect on airspace size or SCM. In vitro studies showed that PPE was partially inactivated by the MPO system; a 56% loss of elastolytic activity occurred during a 6-min incubation of PPE with the MPO system. This may explain why the MPO system did not exacerbate PPE-induced injury, but it does not explain the lack of enhancement for HNE. A 6-minute incubation of HNE with the MPO system resulted in a nonsignificant 10% decrease of elastolytic activity. The failure to demonstrate enhancement of HNE-induced emphysema in the hamster by MPO system-generated oxidants instilled intratra- cheally does not exclude the possibility of such an enhancement in microenvironments of the lungs or under conditions in which hemorrhage is minimized.
- Human neutrophil elastase
- Oxidant impairment of alpha-l-protease inhibitor
- Porcine pancreatic elastase
- Pulmonary emphysema (pathophysiology)
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine