Endotoxin priming of the cyclooxygenase-2-thromboxane axis in isolated rat lungs.
Endotoxin priming of the cyclooxygenase-2-thromboxane axis in isolated rat lungs.
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离体大鼠肺中环氧合酶-2-血栓烷轴的内毒素引发。
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
L. Ermert
中科院分区：
文献类型：
--
作者：
M. Ermert;M. Merkle;R. Mootz;F. Grimminger;Werner Seeger;L. Ermert
前列腺素生成增强与内毒素血症和脓毒症期间发生的血管异常有关，肺特别容易发生此类事件。前列腺素类是由花生四烯酸（AA）通过环氧合酶（考克斯）-1或-2产生的，这两种同工酶最近被证明在不同的肺细胞类型中表达。考克斯的上调可能是内毒素[脂多糖（LPS）]暴露的肺对二次施加的刺激（引发）显示显著增强的血管收缩反应的现象的基础。在不存在和存在1.5%大鼠血浆的情况下，用生理盐缓冲溶液灌注分离的大鼠肺，并在2小时的引发期间暴露于不同浓度的LPS（1，000或10，000 ng/ml）。在此期间没有观察到生理变量的变化，尽管与不存在LPS的对照肺相比，血栓烷（Tx）A（2）和PGI（2）以及肿瘤坏死因子（TNF）-α的基线释放明显增强。LPS引发导致AA诱导的肺动脉压、通气压和肺增重显著升高。在缓冲液灌注液中发现TxA（2）水平同时升高。在缓冲液和缓冲液血浆灌注肺中，所有变化均被三种选择性、结构无关的考克斯-2抑制剂（NS-398、DUP-697和SC-236）在很大程度上抑制。抗TNF-α中和抗体在缓冲液灌注条件下无效。在血浆成分的存在下，TNF-α的产生增加了许多倍，抗TNF-α抗体显著抑制通气压的增加，但不抑制血管升压反应和肺水肿的形成。我们的结论是，LPS致敏的肺对二次施加刺激的反应倾向于增强血管收缩、水肿形成和支气管收缩，几乎完全通过考克斯-2和增加Tx形成进行，TNF-α的产生参与了血浆成分存在下支气管反应性的变化。在最近的免疫组织学研究的背景下，LPS诱导的上调血管和支气管平滑肌细胞中的考克斯-2-血栓烷合酶轴被认为是这些事件的基础。
Enhanced prostanoid generation has been implicated in vascular abnormalities occurring during endotoxemia and sepsis, and the lung is particularly prone to such events. Prostanoids are generated from arachidonic acid (AA) via cyclooxygenase (COX)-1 or -2, both isoenzymes recently demonstrated to be expressed in different lung cell types. Upregulation of COX may underlie the phenomenon that endotoxin [lipopolysaccharide (LPS)]-exposed lungs show markedly enhanced vasoconstrictor responses to secondarily applied stimuli (priming). Isolated rat lungs were perfused with a physiological salt buffer solution in the absence and presence of 1.5% rat plasma and exposed to different concentrations of LPS (1,000 or 10,000 ng/ml) during a 2-h priming period. No change in physiological variables was noted during this period, although enhanced baseline liberation of both thromboxane (Tx) A(2) and PGI(2) as well as of tumor necrosis factor (TNF)-alpha was evident compared with that in control lungs in the absence of LPS. LPS priming caused a significant elevation in AA-induced pulmonary arterial pressure, ventilation pressure, and lung weight gain. Concomitant increased levels of TxA(2) were found in the buffer perfusate. All changes were largely suppressed by three selective, structurally unrelated COX-2 inhibitors (NS-398, DUP-697, and SC-236) in both buffer- and buffer-plasma-perfused lungs. Anti-TNF-alpha neutralizing antibodies were ineffective under conditions of buffer perfusion. In the presence of plasma components, manyfold augmented TNF-alpha generation was noted, and anti-TNF-alpha antibodies significantly suppressed the increase in ventilation pressure but not in the vascular pressor response and lung edema formation. We conclude that the propensity of LPS-primed lungs to respond with enhanced vasoconstriction, edema formation, and bronchoconstriction to a secondarily applied stimulus proceeds nearly exclusively via COX-2 and increased Tx formation, with TNF-alpha generation being involved in the change in bronchomotor reactivity in the presence of plasma constituents. In context with recent immunohistological investigations, LPS-induced upregulation of the COX-2-thromboxane synthase axis in vascular and bronchial smooth muscle cells is suggested to underlie these events.
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影响因子：
--
作者：
L. Crofford
通讯作者：
L. Crofford
影响因子：
56.9
作者：
WRIGHT, SD;RAMOS, RA;MATHISON, JC
通讯作者：
MATHISON, JC
α-凝血酶诱导的肺血管收缩。
DOI：
10.1152/jappl.1987.63.5.1993
发表时间：
1987
期刊：
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子：
--
作者：
Horgan,MJ;Fenton2nd,JW;Malik,AB
通讯作者：
Malik,AB
影响因子：
15.9
作者：
MARTIN, TR;MATHISON, JC;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
15.9
作者：
HARRIS, RC;MCKANNA, JA;BREYER, MD
通讯作者：
BREYER, MD