Respiration
Original Paper
Oxidants from Neutrophil Myeloperoxidase Do not Enhance Elastase-lnduced Emphysema in the HamsterStone P.J.b · Lucey E.C.d · Breuer R.e · Christensen T.G.c · Zaslow M.C.a · Clark R.A.f · Franzblau C.b · Snider G.L.a,daPulmonary Center and Departments of bBiochemistry and cPathology, dBoston University School of Medicine and dthe Pulmonary Section, Boston Department of Veteran Affairs Medical Center, Boston, Mass., USA; ePulmonary Institute, Hebrew University- Hadassah Medical School, Jerusalem, Israel; fIowa City Department of Veteran Affairs Medical Center and Department of Medicine, University of Iowa School of Medicine, Iowa City, Iowa, USA
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Article / Publication Details
Received: December 01, 1992
Accepted: May 05, 1993
Published online: January 20, 2009
Issue release date: 1993
Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 0
ISSN: 0025-7931 (Print)
eISSN: 1423-0356 (Online)
For additional information: https://www.karger.com/RES
Abstract
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 intratracheally does not exclude the possibility of such an enhancement in microenvironments of the lungs or under conditions in which hemorrhage is minimized.
© 1993 S. Karger AG, Basel
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Article / Publication Details
Received: December 01, 1992
Accepted: May 05, 1993
Published online: January 20, 2009
Issue release date: 1993
Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 0
ISSN: 0025-7931 (Print)
eISSN: 1423-0356 (Online)
For additional information: https://www.karger.com/RES
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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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