Geiger M, Stone A, Mason S N, Oldham K T, Guice K S
Division of General Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Am J Physiol. 1997 Jul;273(1 Pt 1):L275-81. doi: 10.1152/ajplung.1997.273.1.L275.
Phenotypic heterogeneity among endothelial cell populations may account for important organ-specific behaviors. Experimental evidence suggests that endothelium-derived nitric oxide mediates certain of these unique responses. The purpose of these investigations was to compare rat pulmonary microvascular endothelial cells with pulmonary artery and aortic macrovascular endothelial cells in their ability to generate nitric oxide (NO). Cultures of these microvascular and macrovascular endothelial cells were incubated with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and Salmonella typhimurium lipopolysaccharide (LPS) alone or in combination, and nitrite production was measured. Single-agent exposure with IFN-gamma (up to 1,000 U/ml), TNF-alpha (up to 60,000 U/ml), or LPS (up to 500 ng/ml) had little effect on nitrite generation. Nitrite production by rat aortic macrovascular endothelial cells (RAEC) was significantly greater than that by the rat lung microvascular endothelial cells (RLMVEC) when stimulated with TNF-alpha + IFN-gamma, LPS + IFN-gamma, or TNF-alpha + LPS. The maximal response by all endothelial cell types (approximately 15-fold increase in RAEC and 8-fold increase in RLMVEC) was observed with LPS + IFN-gamma. The nitrite generation from rat pulmonary artery endothelial cells was intermediate between RAEC and RLMVEC responses when stimulated with IFN-gamma + LPS or TNF-alpha. Similar patterns of heterogeneous inducible nitric oxide synthase mRNA induction occurred when Northern analysis of specimens from the cultured endothelial cell types was done. These data suggest that phenotypic heterogeneity between these endothelial cell populations is substantial and, by inference, that site-specific NO. generation may occur.
内皮细胞群体之间的表型异质性可能解释重要的器官特异性行为。实验证据表明，内皮衍生的一氧化氮介导了其中某些独特反应。这些研究的目的是比较大鼠肺微血管内皮细胞与肺动脉和主动脉大血管内皮细胞产生一氧化氮（NO）的能力。将这些微血管和大血管内皮细胞培养物单独或联合用γ干扰素（IFN-γ）、肿瘤坏死因子-α（TNF-α）和鼠伤寒沙门氏菌脂多糖（LPS）孵育，并测量亚硝酸盐生成量。单独用IFN-γ（高达1000 U/ml）、TNF-α（高达60000 U/ml）或LPS（高达500 ng/ml）处理对亚硝酸盐生成影响很小。当用TNF-α + IFN-γ、LPS + IFN-γ或TNF-α + LPS刺激时，大鼠主动脉大血管内皮细胞（RAEC）产生的亚硝酸盐明显多于大鼠肺微血管内皮细胞（RLMVEC）。在用LPS + IFN-γ刺激时，所有内皮细胞类型的最大反应（RAEC增加约15倍，RLMVEC增加约8倍）被观察到。当用IFN-γ + LPS或TNF-α刺激时，大鼠肺动脉内皮细胞的亚硝酸盐生成介于RAEC和RLMVEC反应之间。对培养的内皮细胞类型标本进行Northern分析时，也出现了类似的异质性诱导型一氧化氮合酶mRNA诱导模式。这些数据表明，这些内皮细胞群体之间的表型异质性很大，据此推断，可能会发生位点特异性NO生成。
