Pentoxifylline reduces injury to isolated lungs perfused with human neutrophils

Ruth J McDonald

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Neutrophils and neutrophil-derived oxidants have been implicated in the development of acute lung injury such as that seen in the adult respiratory distress syndrome (ARDS), in bronchopulmonary dysplasia (BPD), and in animal models of lung injury, including the isolated perfused lung. Both neutrophil- derived oxidant production and retention of neutrophils in the lung are required for injury in this model. Pentoxifylline can reduce lung injury from sepsis in the guinea pig and endotoxin-induced neutrophil sequestration and lung injury in the dog. It is also known to increase neutrophil deformability, which may affect retention in the pulmonary microvasculature. We evaluated neutrophil oxidant production, retention in isolated lungs, and neutrophil-mediated acute lung injury after phorbol myristate acetate (PMA) in the presence of pentoxifylline. Pentoxifylline (2 mM) significantly reduced superoxide anion and hydrogen peroxide production in vitro from PMA- stimulated neutrophils when pentoxifylline was directly added to the incubation mixtures, but not when neutrophils were preincubated with the agent. Pentoxifylline did not reduce retention of neutrophils in isolated lungs as determined by infusion of 111In-labeled neutrophils and gamma counting. Pentoxifylline prevented increases in total lung weight, lung-to- body-weight ratio, and perfusate thromboxane concentrations when it was present in perfusate buffer, whether or not neutrophils were preincubated in pentoxifylline prior to infusion into the lung. Pentoxifylline did not reduce injury to lungs perfused with glucose and glucose oxidase. We conclude that pentoxifylline reduces neutrophil oxidant production and neutrophil-dependent lung injury.

Original languageEnglish (US)
Pages (from-to)1347-1350
Number of pages4
JournalAmerican Review of Respiratory Disease
Volume144
Issue number6
StatePublished - 1991

Fingerprint

Pentoxifylline
Neutrophils
Lung
Wounds and Injuries
Lung Injury
Oxidants
Acute Lung Injury
Tetradecanoylphorbol Acetate
Bronchopulmonary Dysplasia
Glucose Oxidase
Thromboxanes
Adult Respiratory Distress Syndrome
Microvessels
Endotoxins
Superoxides

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Pentoxifylline reduces injury to isolated lungs perfused with human neutrophils. / McDonald, Ruth J.

In: American Review of Respiratory Disease, Vol. 144, No. 6, 1991, p. 1347-1350.

Research output: Contribution to journalArticle

@article{773a857fa7cd453b997fbbaef3c113cd,
title = "Pentoxifylline reduces injury to isolated lungs perfused with human neutrophils",
abstract = "Neutrophils and neutrophil-derived oxidants have been implicated in the development of acute lung injury such as that seen in the adult respiratory distress syndrome (ARDS), in bronchopulmonary dysplasia (BPD), and in animal models of lung injury, including the isolated perfused lung. Both neutrophil- derived oxidant production and retention of neutrophils in the lung are required for injury in this model. Pentoxifylline can reduce lung injury from sepsis in the guinea pig and endotoxin-induced neutrophil sequestration and lung injury in the dog. It is also known to increase neutrophil deformability, which may affect retention in the pulmonary microvasculature. We evaluated neutrophil oxidant production, retention in isolated lungs, and neutrophil-mediated acute lung injury after phorbol myristate acetate (PMA) in the presence of pentoxifylline. Pentoxifylline (2 mM) significantly reduced superoxide anion and hydrogen peroxide production in vitro from PMA- stimulated neutrophils when pentoxifylline was directly added to the incubation mixtures, but not when neutrophils were preincubated with the agent. Pentoxifylline did not reduce retention of neutrophils in isolated lungs as determined by infusion of 111In-labeled neutrophils and gamma counting. Pentoxifylline prevented increases in total lung weight, lung-to- body-weight ratio, and perfusate thromboxane concentrations when it was present in perfusate buffer, whether or not neutrophils were preincubated in pentoxifylline prior to infusion into the lung. Pentoxifylline did not reduce injury to lungs perfused with glucose and glucose oxidase. We conclude that pentoxifylline reduces neutrophil oxidant production and neutrophil-dependent lung injury.",
author = "McDonald, {Ruth J}",
year = "1991",
language = "English (US)",
volume = "144",
pages = "1347--1350",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "6",

}

TY - JOUR

T1 - Pentoxifylline reduces injury to isolated lungs perfused with human neutrophils

AU - McDonald, Ruth J

PY - 1991

Y1 - 1991

N2 - Neutrophils and neutrophil-derived oxidants have been implicated in the development of acute lung injury such as that seen in the adult respiratory distress syndrome (ARDS), in bronchopulmonary dysplasia (BPD), and in animal models of lung injury, including the isolated perfused lung. Both neutrophil- derived oxidant production and retention of neutrophils in the lung are required for injury in this model. Pentoxifylline can reduce lung injury from sepsis in the guinea pig and endotoxin-induced neutrophil sequestration and lung injury in the dog. It is also known to increase neutrophil deformability, which may affect retention in the pulmonary microvasculature. We evaluated neutrophil oxidant production, retention in isolated lungs, and neutrophil-mediated acute lung injury after phorbol myristate acetate (PMA) in the presence of pentoxifylline. Pentoxifylline (2 mM) significantly reduced superoxide anion and hydrogen peroxide production in vitro from PMA- stimulated neutrophils when pentoxifylline was directly added to the incubation mixtures, but not when neutrophils were preincubated with the agent. Pentoxifylline did not reduce retention of neutrophils in isolated lungs as determined by infusion of 111In-labeled neutrophils and gamma counting. Pentoxifylline prevented increases in total lung weight, lung-to- body-weight ratio, and perfusate thromboxane concentrations when it was present in perfusate buffer, whether or not neutrophils were preincubated in pentoxifylline prior to infusion into the lung. Pentoxifylline did not reduce injury to lungs perfused with glucose and glucose oxidase. We conclude that pentoxifylline reduces neutrophil oxidant production and neutrophil-dependent lung injury.

AB - Neutrophils and neutrophil-derived oxidants have been implicated in the development of acute lung injury such as that seen in the adult respiratory distress syndrome (ARDS), in bronchopulmonary dysplasia (BPD), and in animal models of lung injury, including the isolated perfused lung. Both neutrophil- derived oxidant production and retention of neutrophils in the lung are required for injury in this model. Pentoxifylline can reduce lung injury from sepsis in the guinea pig and endotoxin-induced neutrophil sequestration and lung injury in the dog. It is also known to increase neutrophil deformability, which may affect retention in the pulmonary microvasculature. We evaluated neutrophil oxidant production, retention in isolated lungs, and neutrophil-mediated acute lung injury after phorbol myristate acetate (PMA) in the presence of pentoxifylline. Pentoxifylline (2 mM) significantly reduced superoxide anion and hydrogen peroxide production in vitro from PMA- stimulated neutrophils when pentoxifylline was directly added to the incubation mixtures, but not when neutrophils were preincubated with the agent. Pentoxifylline did not reduce retention of neutrophils in isolated lungs as determined by infusion of 111In-labeled neutrophils and gamma counting. Pentoxifylline prevented increases in total lung weight, lung-to- body-weight ratio, and perfusate thromboxane concentrations when it was present in perfusate buffer, whether or not neutrophils were preincubated in pentoxifylline prior to infusion into the lung. Pentoxifylline did not reduce injury to lungs perfused with glucose and glucose oxidase. We conclude that pentoxifylline reduces neutrophil oxidant production and neutrophil-dependent lung injury.

UR - http://www.scopus.com/inward/record.url?scp=0026322729&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026322729&partnerID=8YFLogxK

M3 - Article

C2 - 1660229

AN - SCOPUS:0026322729

VL - 144

SP - 1347

EP - 1350

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 6

ER -