ROLES OF NEUTROPHIL ELASTASE AND SUPEROXIDE ANION IN LEUKOTRIENE B-4-INDUCED LUNG INJURY IN RABBIT

被引:103
作者
YOSHIMURA, K [1 ]
NAKAGAWA, S [1 ]
KOYAMA, S [1 ]
KOBAYASHI, T [1 ]
HOMMA, T [1 ]
机构
[1] SHINSHU UNIV,SCH MED,DEPT INTERNAL MED 1,MATSUMOTO,NAGANO 390,JAPAN
关键词
ISOLATED PERFUSED LUNGS; PULMONARY MICROVASCULAR PERMEABILITY; FILTRATION COEFFICIENT; SUPEROXIDE DISMUTASE;
D O I
10.1152/jappl.1994.76.1.91
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The effects of a competitive neutrophil elastase (NE) inhibitor, ONO-5046, and a recombinant human superoxide dismutase on leukotriene B-4 (LTB(4))-induced polymorphonuclear leukocyte (PMN)-mediated increase in microvascular permeability in isolated non-blood-perfused rabbit lungs were studied. Pulmonary microvascular permeability and lung edema were evaluated by use of the fluid filtration coefficient (K-f) and the wet-to-dry lung weight ratio (W/D), respectively. Pulmonary capillary pressure was estimated by the double occlusion technique. NE activity in the perfusate was determined using a spectrophotometric method. The PMNs (2-3 X 10(8) cells) were added into the perfusate in all groups of lungs. Injection of LTB(4) (5 mu g) increased K-f and W/D without affecting pulmonary arterial or capillary pressure. The LTB(4)-induced lung injury was closely associated with the increase in NE activity in the perfusate. Infusion of ONO-5046 (1 or 10 mg.kg(-1).h(-1)) inhibited the LTB(4)-induced increases in K-f, W/D, and perfusate ate NE activity in a dose-dependent fashion. Infusion of recom binant human superoxide dismutase (80,000 U.kg(-1).h(-1)) attenuated the LTB(4)-induced increases in K-f and W/D, although it did not influence the elevation of perfusate NE activity induced by LTB(4). These results suggest that both NE and superoxide anion play important roles in the LTB(4)-induced PMN-mediated increase in pulmonary microvascular permeability.
引用
收藏
页码:91 / 96
页数:6
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