OXYGEN METABOLITES STIMULATE RELEASE OF HIGH-MOLECULAR-WEIGHT GLYCOCONJUGATES BY CELL AND ORGAN-CULTURES OF RODENT RESPIRATORY EPITHELIUM VIA AN ARACHIDONIC ACID-DEPENDENT MECHANISM
OXYGEN METABOLITES STIMULATE RELEASE OF HIGH-MOLECULAR-WEIGHT GLYCOCONJUGATES BY CELL AND ORGAN-CULTURES OF RODENT RESPIRATORY EPITHELIUM VIA AN ARACHIDONIC ACID-DEPENDENT MECHANISM
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DOI：
10.1172/jci114436
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发表时间：
1990-01-01
影响因子：
15.9
通讯作者：
REPINE, JE
中科院分区：
文献类型：
--
作者：
ADLER, KB;HOLDENSTAUFFER, WJ;REPINE, JE
以粘液过度分泌和呼吸道阻塞为特征的几种常见的肺部疾病可能与呼吸道中吸入或内源性产生的氧化剂(O2代谢物)水平增加有关。我们在体外发现O2代谢产物通过参与花生四烯酸环氧合酶代谢的机制来抑制呼吸道上皮细胞释放高分子量糖共轭化合物(HMG)。化学产生的O2代谢产物(嘌呤+黄嘌呤氧化酶)的非细胞溶解浓度可刺激啮齿动物呼吸道上皮细胞和外植体培养的HMG释放，这种作用可被特定的O2代谢产物清除剂或花生四烯酸代谢抑制剂共同抑制。在上皮细胞中加入O2代谢物可刺激PGF2a的产生，这种作用也可被O2代谢物清除剂或花生四烯酸代谢抑制剂共同抑制。最后，在细胞培养中加入外源PGF2a可刺激HMG的释放。我们认为，O2代谢产物通过参与花生四烯酸的环氧合酶代谢，主要产生PGF2a，从而促进呼吸HMG的释放。这一机制可能是与粘液和/或其他上皮液高分泌相关的各种肺部疾病的基本发病机制，以及细胞对氧化剂增加的基本反应。
Several common pulmonary disorders characterized by mucus hypersecretion and airway obstruction may relate to increased levels of inhaled or endogenously generated oxidants (O2 metabolites) in the respiratory tract. We found that O2 metabolites stumulated release of high-molecular-weight glycoconjugates (HMG) by respiratory epithelial cells in vitro through a mechanism involving cyclooxygenase metabolism of arachidonic acid. Noncytolytic concentrations of chemically generated O2 metabolites (purine + xanthine oxidase) stimulated HMG release by cell and explant cultures of rodent airway epithelium, an effect which is inhibitable by coaddition of specific O2 metabolite scavengers or inhibitors of arachidonic acid metabolism. Addition of O2 metabolites to epithelial cells provoked production of PGF2a, an effect also inhibitable by coaddition of O2 metabolite scavengers or inhibitors of arachidonic acid metabolism. Finally, addition of exogenous PGF2a to cell cultures stimulated HMG release. We conclude that O2 metabolites increase release of respiratory HMG through a mechanism involving cyclooxygenase metabolism of arachidonic acid with production mainly of PGF2a. This mechanism may be fundamental to the pathogenesis of a variety of lung diseases associated with hypersecretion of mucus and/or other epithelial fluids, as well as a basic cellular response to increased oxidants.