Pj. Stone et al., OXIDANTS FROM NEUTROPHIL MYELOPEROXIDASE DO NOT ENHANCE ELASTASE-INDUCED EMPHYSEMA IN THE HAMSTER, Respiration, 60(3), 1993, pp. 137-143
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.