Role of neutrophils in xanthine/xanthine oxidase-induced oxidant injury in isolated rabbit lungs

Departments of 1  Anesthesiology and 2  Internal Medicine, and 3  Cell and Molecular Biology Program, Saint Louis University School of Medicine, St. Louis, Missouri 63110 Reactive oxygen species have been shown to play an important role in the pathogenesis of lung injury. This study was designed to...

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Veröffentlicht in:Journal of applied physiology (1985) 1999-12, Vol.87 (6), p.2319-2325
Hauptverfasser: Kishi, Masashi, Richard, Lois F, Webster, Robert O, Dahms, Thomas E
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container_issue 6
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container_title Journal of applied physiology (1985)
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creator Kishi, Masashi
Richard, Lois F
Webster, Robert O
Dahms, Thomas E
description Departments of 1  Anesthesiology and 2  Internal Medicine, and 3  Cell and Molecular Biology Program, Saint Louis University School of Medicine, St. Louis, Missouri 63110 Reactive oxygen species have been shown to play an important role in the pathogenesis of lung injury. This study was designed to clarify the role of intrapulmonary neutrophils in the development of xanthine/xanthine oxidase (X/XO)-induced lung injury in isolated buffer-perfused rabbit lungs. We measured microvascular fluid filtration coefficient ( K f ) and wet-to-dry weight ratio to assess lung injury. X/XO induced a significant increase in K f and wet-to-dry weight ratio in neutrophil-replete lungs, whereas the lung injury was attenuated in neutrophil-depleted lungs. A neutrophil elastase inhibitor, ONO-5046, also attenuated the lung injury. In addition, X/XO induced a transient pulmonary arterial pressure (P pa ) increase. The thromboxane inhibitor OKY-046 attenuated the P pa increase but did not alter the increase in permeability. Neutrophil depletion reduced the K f increase but had no effect on the P pa increase. These results suggest that intrapulmonary neutrophils activated by X/XO play a major role in development of the lung injury, that neutrophil elastase is involved in the injury, and that the X/XO-induced vasoconstriction is independent of intrapulmonary neutrophils. permeability; neutrophil elastase; perfused lungs
doi_str_mv 10.1152/jappl.1999.87.6.2319
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This study was designed to clarify the role of intrapulmonary neutrophils in the development of xanthine/xanthine oxidase (X/XO)-induced lung injury in isolated buffer-perfused rabbit lungs. We measured microvascular fluid filtration coefficient ( K f ) and wet-to-dry weight ratio to assess lung injury. X/XO induced a significant increase in K f and wet-to-dry weight ratio in neutrophil-replete lungs, whereas the lung injury was attenuated in neutrophil-depleted lungs. A neutrophil elastase inhibitor, ONO-5046, also attenuated the lung injury. In addition, X/XO induced a transient pulmonary arterial pressure (P pa ) increase. The thromboxane inhibitor OKY-046 attenuated the P pa increase but did not alter the increase in permeability. Neutrophil depletion reduced the K f increase but had no effect on the P pa increase. These results suggest that intrapulmonary neutrophils activated by X/XO play a major role in development of the lung injury, that neutrophil elastase is involved in the injury, and that the X/XO-induced vasoconstriction is independent of intrapulmonary neutrophils. permeability; neutrophil elastase; perfused lungs</description><identifier>ISSN: 8750-7587</identifier><identifier>EISSN: 1522-1601</identifier><identifier>DOI: 10.1152/jappl.1999.87.6.2319</identifier><identifier>PMID: 10601184</identifier><identifier>CODEN: JAPHEV</identifier><language>eng</language><publisher>Bethesda, MD: Am Physiological Soc</publisher><subject>Animals ; Biological and medical sciences ; Blood Pressure - drug effects ; Capillary Permeability - drug effects ; Drug Combinations ; Edema - chemically induced ; Edema - pathology ; Edema - physiopathology ; In Vitro Techniques ; Lung - enzymology ; Lung - pathology ; Lung - physiopathology ; Lung Diseases - chemically induced ; Lung Diseases - pathology ; Lung Diseases - physiopathology ; Lungs ; Medical sciences ; Neutrophils - physiology ; Oxidants - pharmacology ; Oxygen ; Peroxidase - metabolism ; Pneumology ; Pulmonary Artery - physiopathology ; Pulmonary Circulation - drug effects ; Rabbits ; Respiratory system : syndromes and miscellaneous diseases ; Vasoconstriction - drug effects ; Xanthine - pharmacology ; Xanthine Oxidase - pharmacology</subject><ispartof>Journal of applied physiology (1985), 1999-12, Vol.87 (6), p.2319-2325</ispartof><rights>2000 INIST-CNRS</rights><rights>Copyright American Physiological Society Dec 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-67fa153e78ef391c938d91662fd83462fc0e7c95035a7e99539a42b217135bf93</citedby><cites>FETCH-LOGICAL-c437t-67fa153e78ef391c938d91662fd83462fc0e7c95035a7e99539a42b217135bf93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3039,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=1230980$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10601184$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kishi, Masashi</creatorcontrib><creatorcontrib>Richard, Lois F</creatorcontrib><creatorcontrib>Webster, Robert O</creatorcontrib><creatorcontrib>Dahms, Thomas E</creatorcontrib><title>Role of neutrophils in xanthine/xanthine oxidase-induced oxidant injury in isolated rabbit lungs</title><title>Journal of applied physiology (1985)</title><addtitle>J Appl Physiol (1985)</addtitle><description>Departments of 1  Anesthesiology and 2  Internal Medicine, and 3  Cell and Molecular Biology Program, Saint Louis University School of Medicine, St. Louis, Missouri 63110 Reactive oxygen species have been shown to play an important role in the pathogenesis of lung injury. This study was designed to clarify the role of intrapulmonary neutrophils in the development of xanthine/xanthine oxidase (X/XO)-induced lung injury in isolated buffer-perfused rabbit lungs. We measured microvascular fluid filtration coefficient ( K f ) and wet-to-dry weight ratio to assess lung injury. X/XO induced a significant increase in K f and wet-to-dry weight ratio in neutrophil-replete lungs, whereas the lung injury was attenuated in neutrophil-depleted lungs. A neutrophil elastase inhibitor, ONO-5046, also attenuated the lung injury. In addition, X/XO induced a transient pulmonary arterial pressure (P pa ) increase. The thromboxane inhibitor OKY-046 attenuated the P pa increase but did not alter the increase in permeability. Neutrophil depletion reduced the K f increase but had no effect on the P pa increase. 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This study was designed to clarify the role of intrapulmonary neutrophils in the development of xanthine/xanthine oxidase (X/XO)-induced lung injury in isolated buffer-perfused rabbit lungs. We measured microvascular fluid filtration coefficient ( K f ) and wet-to-dry weight ratio to assess lung injury. X/XO induced a significant increase in K f and wet-to-dry weight ratio in neutrophil-replete lungs, whereas the lung injury was attenuated in neutrophil-depleted lungs. A neutrophil elastase inhibitor, ONO-5046, also attenuated the lung injury. In addition, X/XO induced a transient pulmonary arterial pressure (P pa ) increase. The thromboxane inhibitor OKY-046 attenuated the P pa increase but did not alter the increase in permeability. Neutrophil depletion reduced the K f increase but had no effect on the P pa increase. 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subjects Animals
Biological and medical sciences
Blood Pressure - drug effects
Capillary Permeability - drug effects
Drug Combinations
Edema - chemically induced
Edema - pathology
Edema - physiopathology
In Vitro Techniques
Lung - enzymology
Lung - pathology
Lung - physiopathology
Lung Diseases - chemically induced
Lung Diseases - pathology
Lung Diseases - physiopathology
Lungs
Medical sciences
Neutrophils - physiology
Oxidants - pharmacology
Oxygen
Peroxidase - metabolism
Pneumology
Pulmonary Artery - physiopathology
Pulmonary Circulation - drug effects
Rabbits
Respiratory system : syndromes and miscellaneous diseases
Vasoconstriction - drug effects
Xanthine - pharmacology
Xanthine Oxidase - pharmacology
title Role of neutrophils in xanthine/xanthine oxidase-induced oxidant injury in isolated rabbit lungs
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