Effect of immunologic mediators on rat pulmonary Endothelial Cell (EC) and rat lung xanthine dehydrogenase/xanthine oxidase: Role of nitric oxide and oxygen

Claudia G. Cote, J. J. Zulueta, Paul M Hassoun

Research output: Contribution to journalArticle

Abstract

Purpose: To examine the modulating role of nitric oxide (NO) on the activation of xanthine dehydrogenase/xanthine oxidase (XD/XO) by cytokines, in hypoxia (3% O2) and normoxia (20% O2). Methods: We exposed rat pulmonary EC to normoxia or hypoxia, in the presence or absence of LPS (10 μg/ml), IL-1 (0.5 ng/ml), and L-NAME (300 μM), either alone or in combination. In separate experiments, we exposed male adult Sprague-Dawley rats to either a normobaric or hypobaric atmosphere (0.5 atm, simulated hypoxia), and to LPS (1 mg/kg) and Il-1 (100 μg/kg) alone or in combination. Results: In vitro, hypoxia alone and the combination of LPS and IL-1 cause a 2-fold increase in EC XD/XO activity as compared to normoxic cells. Simultaneous treatment of EC with hypoxia and LPS+IL-1 causes a 5-fold increase in activity as compared to normoxic EC unstimulated by cytokines. Inhibition of NO synthase by L-NAME causes a further increase in XD/XO activity in each treatment group. Similarly, animals exposed to hypoxia show a significant increase in lung XD/XO compared to normoxic animals. Simultaneous treatment with LPS and IL-1 significantly increases tissue XD/XO above levels seen with hypoxia alone. Conclusions: Our results indicate that certain immunologic mediators are capable of inducing XD/XO enzymatic activity and that this effect is more pronounced with exposure to hypoxia. In vitro, nitric oxide inhibitors potentiate the stimulatory effect of cytokines, suggesting a modulatory effect of nitric oxide. Clinical Implications: XO has been implicated as a major source for reactive oxygen species, particularly during conditions associated with ischemia-reperfusion or hypoxia-reoxygenation. Our findings suggest an intricate regulatory loop linking XD/XO, O2, NO, and cytokines which could play a role in the pathophysiology of disorders associated with hypoxia and circulating cytokines, such as the adult respiratory distress syndrome.

Original languageEnglish (US)
JournalChest
Volume110
Issue number4 SUPPL.
StatePublished - Oct 1996
Externally publishedYes

Fingerprint

Xanthine Dehydrogenase
Xanthine Oxidase
Nitric Oxide
Endothelial Cells
Oxygen
Lung
Interleukin-1
Cytokines
NG-Nitroarginine Methyl Ester
Hypoxia
Cell Hypoxia
Adult Respiratory Distress Syndrome
Atmosphere
Nitric Oxide Synthase
Reperfusion
Sprague Dawley Rats
Reactive Oxygen Species
Ischemia

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Effect of immunologic mediators on rat pulmonary Endothelial Cell (EC) and rat lung xanthine dehydrogenase/xanthine oxidase : Role of nitric oxide and oxygen. / Cote, Claudia G.; Zulueta, J. J.; Hassoun, Paul M.

In: Chest, Vol. 110, No. 4 SUPPL., 10.1996.

Research output: Contribution to journalArticle

@article{cd1d3c221d3e407cbcdb4eef7d7668e9,
title = "Effect of immunologic mediators on rat pulmonary Endothelial Cell (EC) and rat lung xanthine dehydrogenase/xanthine oxidase: Role of nitric oxide and oxygen",
abstract = "Purpose: To examine the modulating role of nitric oxide (NO) on the activation of xanthine dehydrogenase/xanthine oxidase (XD/XO) by cytokines, in hypoxia (3{\%} O2) and normoxia (20{\%} O2). Methods: We exposed rat pulmonary EC to normoxia or hypoxia, in the presence or absence of LPS (10 μg/ml), IL-1 (0.5 ng/ml), and L-NAME (300 μM), either alone or in combination. In separate experiments, we exposed male adult Sprague-Dawley rats to either a normobaric or hypobaric atmosphere (0.5 atm, simulated hypoxia), and to LPS (1 mg/kg) and Il-1 (100 μg/kg) alone or in combination. Results: In vitro, hypoxia alone and the combination of LPS and IL-1 cause a 2-fold increase in EC XD/XO activity as compared to normoxic cells. Simultaneous treatment of EC with hypoxia and LPS+IL-1 causes a 5-fold increase in activity as compared to normoxic EC unstimulated by cytokines. Inhibition of NO synthase by L-NAME causes a further increase in XD/XO activity in each treatment group. Similarly, animals exposed to hypoxia show a significant increase in lung XD/XO compared to normoxic animals. Simultaneous treatment with LPS and IL-1 significantly increases tissue XD/XO above levels seen with hypoxia alone. Conclusions: Our results indicate that certain immunologic mediators are capable of inducing XD/XO enzymatic activity and that this effect is more pronounced with exposure to hypoxia. In vitro, nitric oxide inhibitors potentiate the stimulatory effect of cytokines, suggesting a modulatory effect of nitric oxide. Clinical Implications: XO has been implicated as a major source for reactive oxygen species, particularly during conditions associated with ischemia-reperfusion or hypoxia-reoxygenation. Our findings suggest an intricate regulatory loop linking XD/XO, O2, NO, and cytokines which could play a role in the pathophysiology of disorders associated with hypoxia and circulating cytokines, such as the adult respiratory distress syndrome.",
author = "Cote, {Claudia G.} and Zulueta, {J. J.} and Hassoun, {Paul M}",
year = "1996",
month = "10",
language = "English (US)",
volume = "110",
journal = "Chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "4 SUPPL.",

}

TY - JOUR

T1 - Effect of immunologic mediators on rat pulmonary Endothelial Cell (EC) and rat lung xanthine dehydrogenase/xanthine oxidase

T2 - Role of nitric oxide and oxygen

AU - Cote, Claudia G.

AU - Zulueta, J. J.

AU - Hassoun, Paul M

PY - 1996/10

Y1 - 1996/10

N2 - Purpose: To examine the modulating role of nitric oxide (NO) on the activation of xanthine dehydrogenase/xanthine oxidase (XD/XO) by cytokines, in hypoxia (3% O2) and normoxia (20% O2). Methods: We exposed rat pulmonary EC to normoxia or hypoxia, in the presence or absence of LPS (10 μg/ml), IL-1 (0.5 ng/ml), and L-NAME (300 μM), either alone or in combination. In separate experiments, we exposed male adult Sprague-Dawley rats to either a normobaric or hypobaric atmosphere (0.5 atm, simulated hypoxia), and to LPS (1 mg/kg) and Il-1 (100 μg/kg) alone or in combination. Results: In vitro, hypoxia alone and the combination of LPS and IL-1 cause a 2-fold increase in EC XD/XO activity as compared to normoxic cells. Simultaneous treatment of EC with hypoxia and LPS+IL-1 causes a 5-fold increase in activity as compared to normoxic EC unstimulated by cytokines. Inhibition of NO synthase by L-NAME causes a further increase in XD/XO activity in each treatment group. Similarly, animals exposed to hypoxia show a significant increase in lung XD/XO compared to normoxic animals. Simultaneous treatment with LPS and IL-1 significantly increases tissue XD/XO above levels seen with hypoxia alone. Conclusions: Our results indicate that certain immunologic mediators are capable of inducing XD/XO enzymatic activity and that this effect is more pronounced with exposure to hypoxia. In vitro, nitric oxide inhibitors potentiate the stimulatory effect of cytokines, suggesting a modulatory effect of nitric oxide. Clinical Implications: XO has been implicated as a major source for reactive oxygen species, particularly during conditions associated with ischemia-reperfusion or hypoxia-reoxygenation. Our findings suggest an intricate regulatory loop linking XD/XO, O2, NO, and cytokines which could play a role in the pathophysiology of disorders associated with hypoxia and circulating cytokines, such as the adult respiratory distress syndrome.

AB - Purpose: To examine the modulating role of nitric oxide (NO) on the activation of xanthine dehydrogenase/xanthine oxidase (XD/XO) by cytokines, in hypoxia (3% O2) and normoxia (20% O2). Methods: We exposed rat pulmonary EC to normoxia or hypoxia, in the presence or absence of LPS (10 μg/ml), IL-1 (0.5 ng/ml), and L-NAME (300 μM), either alone or in combination. In separate experiments, we exposed male adult Sprague-Dawley rats to either a normobaric or hypobaric atmosphere (0.5 atm, simulated hypoxia), and to LPS (1 mg/kg) and Il-1 (100 μg/kg) alone or in combination. Results: In vitro, hypoxia alone and the combination of LPS and IL-1 cause a 2-fold increase in EC XD/XO activity as compared to normoxic cells. Simultaneous treatment of EC with hypoxia and LPS+IL-1 causes a 5-fold increase in activity as compared to normoxic EC unstimulated by cytokines. Inhibition of NO synthase by L-NAME causes a further increase in XD/XO activity in each treatment group. Similarly, animals exposed to hypoxia show a significant increase in lung XD/XO compared to normoxic animals. Simultaneous treatment with LPS and IL-1 significantly increases tissue XD/XO above levels seen with hypoxia alone. Conclusions: Our results indicate that certain immunologic mediators are capable of inducing XD/XO enzymatic activity and that this effect is more pronounced with exposure to hypoxia. In vitro, nitric oxide inhibitors potentiate the stimulatory effect of cytokines, suggesting a modulatory effect of nitric oxide. Clinical Implications: XO has been implicated as a major source for reactive oxygen species, particularly during conditions associated with ischemia-reperfusion or hypoxia-reoxygenation. Our findings suggest an intricate regulatory loop linking XD/XO, O2, NO, and cytokines which could play a role in the pathophysiology of disorders associated with hypoxia and circulating cytokines, such as the adult respiratory distress syndrome.

UR - http://www.scopus.com/inward/record.url?scp=33750278880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750278880&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33750278880

VL - 110

JO - Chest

JF - Chest

SN - 0012-3692

IS - 4 SUPPL.

ER -