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

Abstract

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.

• Authors: M Kishi, L F Richard, R O Webster, T E Dahms
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 87 Issue 6 Pg. 2319-25 (Dec 1999) ISSN: 8750-7587 [Print] United States
• PMID: 10601184 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Drug Combinations
• Oxidants
• Xanthine
• Peroxidase
• Xanthine Oxidase

Topics

• Animals
• Blood Pressure (drug effects)
• Capillary Permeability (drug effects)
• Drug Combinations
• Edema (chemically induced, pathology, physiopathology)
• In Vitro Techniques
• Lung (enzymology, pathology, physiopathology)
• Lung Diseases (chemically induced, pathology, physiopathology)
• Neutrophils (physiology)
• Oxidants (pharmacology)
• Peroxidase (metabolism)
• Pulmonary Artery (physiopathology)
• Pulmonary Circulation (drug effects)
• Rabbits
• Vasoconstriction (drug effects)
• Xanthine (pharmacology)
• Xanthine Oxidase (pharmacology)