Oxidants from neutrophil myeloperoxidase do not enhance elastase-induced emphysema in the hamster.
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 micrograms 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 micrograms HNE failed to enhance the severity of the SCM or emphysema induced by HNE alone. A second experiment was carried out using 50 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Stone
P J
PJ
Department of Biochemistry, Boston University School of Medicine, Mass 02118.
Lucey
E C
EC
Breuer
R
R
Christensen
T G
TG
Zaslow
M C
MC
Clark
R A
RA
Franzblau
C
C
Snider
G L
GL
D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D006224:Cricetinae; D005949:Glucose Oxidase / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase; D008176:Lung Volume Measurements; D008297:Male; D008647:Mesocricetus; D009504:Neutrophils / Q000201:enzymology*; D016877:Oxidants / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000494:pharmacology*; D009195:Peroxidase / Q000494:pharmacology*; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D002712:Chlorides; D016877:Oxidants; D000515:alpha 1-Antitrypsin; D005949:Glucose Oxidase; D009195:Peroxidase; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase