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

Autor: Kishi, Masashi, Richard, Lois F., Webster, Robert O., Dahms, Thomas E.
Zdroj: Journal of Applied Physiology; December 1999, Vol. 87 Issue: 6 p2319-2325, 7p
Abstrakt: 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 (Kf) and wet-to-dry weight ratio to assess lung injury. X/XO induced a significant increase inKfand 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 (Ppa) increase. The thromboxane inhibitor OKY-046 attenuated the Ppaincrease but did not alter the increase in permeability. Neutrophil depletion reduced theKfincrease but had no effect on the Ppaincrease. 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.
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