Rat pulmonary cyclooxygenase-2 expression in response to endotoxin challenge -: Differential regulation in the various types of cells in the lung
Rat pulmonary cyclooxygenase-2 expression in response to endotoxin challenge -: Differential regulation in the various types of cells in the lung
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DOI：
10.1016/s0002-9440(10)64998-x
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发表时间：
2000-04-01
影响因子：
6
通讯作者：
Seeger, W
中科院分区：
文献类型：
--
作者：
Ermert, L;Ermert, M;Seeger, W
环氧合酶（考克斯）是前列腺素合成的关键酶，由两种异构体考克斯-1和考克斯-2组成，最近发现这两种异构体在大鼠肺组织中组成型表达，具有不同的细胞分布特征。肺考克斯-1和考克斯-2表达的血管内毒素脂多糖（LPS）管理的反应性进行了研究，在隔离，通气大鼠肺，缓冲液灌注与或不与大鼠血浆的混合物。通过先前描述的银增强和外极化图像分析的方法测量免疫组织化学染色强度。在全肺匀浆中定量的考克斯-1 mRNA和考克斯-1的细胞定位在对LPS的响应中均未改变。相反，考克斯-2 mRNA（肺匀浆）发生时间和剂量依赖性上调，并且观察到细胞水平的不同LPS反应性。在支气管上皮细胞、支气管和血管平滑肌细胞、BALT内的细胞和肺门大静脉的肌细胞中，观察到在基线条件下已经表达该酶的细胞类型中的考克斯-2的上调。考克斯-2从头诱导发生在内皮细胞和大多数肺泡巨噬细胞。考克斯-2在血管周围和支气管周围巨噬细胞样细胞中表达下调。此外，注意到血浆成分的不同影响：对于大多数细胞，CD 14表面表达与考克斯-2对LPS的反应性相关，而血浆成分的存在是CD 14阴性细胞中LPS反应的先决条件。LPS不会引起灌注肺的生理变化，但显着增强基线前列腺素的产生。我们的结论是，LPS诱导的考克斯-2调节发生在一个复杂的，细胞特异性的方式，这可能是相关的致病性后遗症，脓毒性肺损伤和急性呼吸衰竭。
Cyclooxygenase (Cox), the key enzyme of prostanoid synthesis, consists of the two isoforms Cox-1 and Cox-2, both recently noted to be constitutively expressed in rat lungs with a distinct profile of cellular distribution. The responsiveness of pulmonary Cox-1 and Cox-2 expression to intravascular endotoxin lipopolysaccharide (LPS) administration was investigated in isolated, ventilated rat lungs, buffer-perfused with or without admixture of rat plasma. Immunohistochemical staining intensity was measured by a previously described method of silver enhancement and epipolarization image analysis, Both the Cox-1 mRNA, quantified in the whole lung homogenate, and the cellular localization of Cox-1 were unchanged in response to LPS, In contrast, time- and dose-dependent up-regulation of Cox-2 mRNA (lung homogenate) occurred, and differential LPS reactivity at the cellular level was observed. Up-regulation of Cox-2 in cell types expressing this enzyme already under baseline conditions was noted in bronchial epithelial cells, bronchial and vascular smooth muscle cells, cells within the BALT and myocytes of the large hilar veins. De novo induction of Cox-2 occurred in endothelial cells and the majority of alveolar macrophages. Down-regulation of Cox-2 was observed in perivascular and peribronchial macrophage-like cells. Moreover, differential impact of plasma components was noted: for the large majority of cells, CD14 surface expression correlated with Cox-2 responsiveness to LPS independent of plasma, whereas the presence of plasma components was a prerequisite for the LPS response in CD14-negative cells. LPS did not provoke physiological changes in the perfused lungs, but markedly enhanced baseline prostanoid generation. We conclude that LPS-induced Cox-2 regulation occurs in a complex, cell-specific manner, which may be relevant for pathogenetic sequelae in septic lung injury and acute respiratory failure.