Inducible nitric oxide synthase - Knockout mice exhibit resistance to pleurisy and lung injury caused by carrageenan
Inducible nitric oxide synthase - Knockout mice exhibit resistance to pleurisy and lung injury caused by carrageenan
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DOI：
10.1164/ajrccm.162.5.9912125
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发表时间：
2000-11-01
影响因子：
24.7
通讯作者：
Caputi, AP
中科院分区：
文献类型：
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作者：
Cuzzocrea, S;Mazzon, E;Caputi, AP
在本研究中，我们通过比较野生型小鼠（WT）和缺乏（敲除[KO]）小鼠的反应，研究了诱导型（或2型）一氧化氮合酶（iNOS）在急性炎症发展中的作用。与经角叉菜胶处理的iNOS-WT小鼠相比，接受角叉菜胶的iNOS-KO小鼠表现出胸膜渗出和多形核细胞迁移程度降低。与iNOSWT小鼠相比，iNOS-KO小鼠的肺髓过氧化物酶（MPO）活性和脂质过氧化反应显著降低。硝基酪氨酸的免疫组织化学分析显示在来自角叉菜胶处理的iNOS-WT小鼠的肺中的阳性染色。角叉菜胶处理的iNOS-WT小鼠的肺组织切片显示聚腺苷二磷酸（ADP）-核糖合成酶阳性染色，主要位于肺泡巨噬细胞和气道上皮细胞中。对角叉菜胶处理的iNOS-KO小鼠的组织切片中硝基酪氨酸和聚ADP-核糖合成酶的染色强度和程度显著降低。iNOS-KO小鼠的发炎肺也显示出改善的组织学状态。此外，在从经受角叉菜胶诱导的胸膜炎的iNOS-KO小鼠的胸膜腔收获的巨噬细胞中，离体观察到能量状态抑制、DNA链断裂和烟酰胺腺嘌呤二核苷酸（NAD（+））细胞水平降低的显著减少。总之，我们的结果清楚地表明，iNOS在急性炎症反应中起着重要作用。
In the present study, we investigated the role of inducible (or type 2) nitric oxide synthase (iNOS) in the development of acute inflammation by comparing the responses in wild-type mice (WT) and mice lacking (knockout [KO]). When compared with carrageenan-treated iNOS-WT mice, iNOS-KO mice that had received carrageenan exhibited a reduced degree of pleural exudation and polymorphonuclear cell migration. Lung myeloperoxidase (MPO) activity and lipid peroxidation were significantly reduced in iNOS-KO mice in comparison with iNOSWT mice. Immunohistochemical analysis for nitrotyrosine revealed positive staining in lungs from carrageenan-treated iNOS-WT mice. Lung tissue sections from carrageenan-treated iNOS-WT mice showed positive staining for poly adenosine diphosphate (ADP)-ribose synthetase that was mainly localized in alveolar macrophages and in airway epithelial cells. The intensity and degree of staining for nitrotyrosine and poly-ADP-ribose synthetase were markedly reduced in tissue sections from carrageenan-treated iNOS-KO mice. The inflamed lungs of iNOS-KO mice also showed an improved histologic status. Furthermore, a significant reduction in the suppression of energy status, in DNA strand breakage, and in decreased cellular levels of nicotinamide adenine dinucleotide (NAD(+)) was observed ex vivo in macrophages harvested from the pleural cavity of iNOS-KO mice subjected to carrageenan-induced pleurisy. Taken together, our results clearly show that iNOS plays an important role in the acute inflammatory response.