NITRIC-OXIDE SYNTHASE IN HUMAN AND RAT LUNG - IMMUNOCYTOCHEMICAL AND HISTOCHEMICAL-LOCALIZATION
NITRIC-OXIDE SYNTHASE IN HUMAN AND RAT LUNG - IMMUNOCYTOCHEMICAL AND HISTOCHEMICAL-LOCALIZATION
复制标题
DOI：
10.1165/ajrcmb/9.4.371
复制
发表时间：
1993-10-01
影响因子：
6.4
通讯作者：
STAMLER, JS
中科院分区：
文献类型：
--
作者：
KOBZIK, L;BREDT, DS;STAMLER, JS
一氧化氮合酶 (NOS) 产生一氧化氮，一氧化氮是肺部众多生理和炎症过程中具有潜在重要性的介质。我们通过用特异性抗体进行免疫过氧化物酶标记或通过 NOS 特征性 NADPH 心肌酶活性的组织化学证明，将组成型 NOS (c-NOS) 和诱导型 NOS (i-NOS) 定位在肺组织内。我们分析了从手术肿瘤切除未涉及区域获得的人体气道 (n = 4) 或实质 (n = 10) 标本。我们还研究了人类胎儿肺样本 (n = 6) 和正常或发炎（气管内 LPS 滴注后 16 小时）大鼠肺组织。使用抗 c-NOS 免疫染色鉴定了大鼠肺神经、内皮和气道上皮中的 c-NOS 抗原。正常或发炎的大鼠巨噬细胞未染色。人类神经元件和大血管内皮显示出抗 c-NOS 的免疫染色，但没有看到气道或肺泡上皮的标记。抗 i-NOS 免疫染色显示，在体内或体外 LPS 处理后，大鼠巨噬细胞出现强烈标记，而正常细胞呈阴性。人肺泡巨噬细胞偶尔呈 i-NOS 阳性，特别是在慢性炎症区域，也显示内皮细胞的局灶性免疫标记。在人支气管和正常大鼠气管样本中发现大的软骨气道上皮细胞均具有抗 i-NOS 标记，这表明与诱导型巨噬细胞型 NOS 共享表位或高度同源的 NOS 具有组成性作用。 NADPH 心肌黄酶活性的组织化学染色与 NOS 抗原的免疫定位一致。结果表明，人和大鼠肺内许多不同的解剖结构含有 NOS，并表明 NOS 活性在肺稳态和炎症中发挥作用。
Nitric oxide synthase (NOS) produces nitric oxide, a mediator of potential importance in numerous physiologic and inflammatory processes in the lung. We localized constitutive NOS (c-NOS) and inducible NOS (i-NOS) within lung tissue by immunoperoxidase labeling with specific antibodies or by histochemical demonstration of the characteristic NADPH diaphorase activity of NOS. We analyzed human airway (n = 4) or parenchyma (n = 10) specimens obtained from uninvolved areas of surgical tumor resections. We also studied human fetal lung samples (n = 6) and normal or inflamed (16 h after intratracheal LPS instillation) rat lung tissue. Immunostaining with anti-c-NOS identified c-NOS antigen in rat lung nerves, endothelium, and airway epithelium. Normal or inflamed rat macrophages were not stained. Human nerve elements and large-vessel endothelium showed immunostaining with the anti-c-NOS, but no labeling of the airway or alveolar epithelium was seen. Immunostaining with anti-i-NOS showed strong labeling of rat macrophages after LPS treatment, in vivo or in vitro, while normals were negative. Human alveolar macrophages were occasionally positive for i-NOS, especially in areas of chronic inflammation, which also showed focal immunolabeling of endothelium. Uniform labeling of epithelium in large, cartilaginous airways was found with anti-i-NOS in both human bronchi and normal rat trachea samples, suggesting a constitutive role for a NOS that shares epitope(s) with or is highly homologous to the inducible, macrophage type of NOS. Histochemical staining for NADPH diaphorase activity was consistent with immunolocalization of NOS antigens. The results indicate that numerous distinct anatomic compartments within human and rat lungs contain NOS, and suggest a role for NOS activity in pulmonary homeostasis and inflammation.