Lung sources and cytokine requirements for in vivo expression of inducible nitric oxide synthase.
Lung sources and cytokine requirements for in vivo expression of inducible nitric oxide synthase.
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诱导型一氧化氮合酶体内表达的肺源和细胞因子需求。
DOI：
10.1165/ajrcmb.12.6.7539274
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Ward,PA
中科院分区：
文献类型：
--
作者：
Warner,RL;Paine3rd,R;Christensen,PJ;Marletta,MA;Richards,MK;Wilcoxen,SE;Ward,PA
已知诱导型一氧化氮合酶（iNOS）的产物参与免疫球蛋白G免疫复合物（IgG-ICx）肺内沉积后的肺损伤。在目前的研究中，大鼠肺泡巨噬细胞在体外刺激与鼠干扰素γ（IFN-γ），肿瘤坏死因子α，白细胞介素1 α，（IL-1 α），脂多糖（LPS），或IgG-ICx免疫染色的iNOS和产生亚硝酸盐/硝酸盐-（NO2-/NO3-）的剂量和时间依赖性的方式需要可用性的L-精氨酸。在相同条件下，IL-4和IL-10可减少NO2-/NO3-的产生。II型肺泡上皮细胞，这是从正常大鼠肺和刺激IgG-ICx，LPS，或IFN-γ体外获得的，也免疫染色的iNOS和产生NO2-/NO3-。采用特殊的支气管肺泡灌洗（BAL）技术回收肺泡巨噬细胞和II型肺泡上皮细胞。在这些条件下，肺内沉积的LPS产生的BAL液含有增加量的NO2-/NO3-和巨噬细胞，自发释放NO2-/NO3-和染色的iNOS。IgG肺内沉积后，巨噬细胞以及II型细胞（BAL回收）自发产生NO2-/NO3-和两种细胞类型的iNOS免疫染色（约20%的所有II型细胞和35%的所有肺泡巨噬细胞）。使用双重荧光染色细胞鉴定，IgG免疫复合物沉积后的肺组织冷冻切片显示肺泡巨噬细胞和II型细胞中的iNOS。最后，在肺泡炎的免疫复合物模型中，巨噬细胞中iNOS的出现以及巨噬细胞体外产生NO2-/NO3-依赖于肿瘤坏死因子α、IL-1和IFN-γ的体内可用性。这些研究表明炎症肺中一氧化氮的双重细胞来源和几种细胞因子对iNOS的需求。
Products of inducible nitric oxide synthase (iNOS) are known to be involved in lung injury following intrapulmonary deposition of immunoglobulin G immune complexes (IgG-ICx). In the current studies rat alveolar macrophages stimulated in vitro with murine interferon gamma (IFN-gamma), tumor necrosis factor alpha, interleukin 1 alpha, (IL-1 alpha), lipopolysaccharide (LPS), or IgG-ICx immunostained for iNOS and produced nitrite/nitrate- (NO2-/NO3-) in a dose- and time-dependent manner requiring availability of L-arginine. Under the same conditions, IL-4 and IL-10 reduced NO2-/NO3- generation. Type II alveolar epithelial cells, which were obtained from normal rat lungs and stimulated in vitro with IgG-ICx, LPS, or IFN-gamma, also immunostained for iNOS and generated NO2-/NO3-. Special techniques of bronchoalveolar lavage (BAL) were used to retrieve alveolar macrophages and type II alveolar epithelial cells. Under these conditions, intrapulmonary deposition of LPS yielded BAL fluids containing increased amounts of NO2-/NO3- and macrophages that spontaneously released NO2-/NO3- and stained for iNOS. After intrapulmonary deposition of IgG both macrophages as well as type II cells (retrieved by BAL) spontaneously produced NO2-/NO3- and both cell types immunostained for iNOS (approximately 20% of all type II cells and 35% of all alveolar macrophages). Using dual fluorescence staining for cell identification, frozen sections of lung tissue after IgG immune complex deposition revealed iNOS in both alveolar macrophages and type II cells. Finally, in the immune complex model of alveolitis, the appearance of iNOS in macrophages as well as macrophage production in vitro of NO2-/NO3- was dependent on the in vivo availability of tumor necrosis factor alpha, IL-1, and IFN-gamma. These studies suggest a dual cell source for nitric oxide in inflamed lungs and the requirements for iNOS of several cytokines.