Arachidonic acid metabolism in airway epithelial cells.
Arachidonic acid metabolism in airway epithelial cells.
复制标题
气道上皮细胞中的花生四烯酸代谢。
DOI：
10.1146/annurev.ph.54.030192.001511
复制
发表时间：
1992
影响因子：
18.2
通讯作者：
Holtzman,MJ
中科院分区：
文献类型：
--
作者：
Holtzman,MJ
气道上皮细胞部分通过激活磷脂酶-脂肪酸氧合途径来发挥其生理作用。最近的发现包括以下事实：（a）气道上皮细胞含有丰富的脂肪酸底物储存，包括花生四烯酸，用于氧合，（B）细胞在特定磷脂酶激活时释放花生四烯酸，（c）细胞含有相对于其它细胞类型高水平的新型环加氧酶和脂氧合酶，和（d）某些花生四烯酸代谢物对气道终末器官如平滑肌、神经、粘液腺和上皮细胞本身具有有效的生物学作用。研究花生四烯酸在气道上皮细胞的代谢往往是在基底细胞、纤毛细胞和杯状细胞的异质细胞群上进行的，因此关于单个细胞类型和细胞分化过程中的变化的信息仍然很难确定。通过跨细胞合成类二十烷酸的潜在细胞-细胞相互作用也需要进一步研究。这些目标中的每一个都将通过使用培养的气道上皮细胞来帮助，但是培养系统已经证明在保留原始组织的氧合表型方面存在问题。上皮细胞对吸入剂的相同访问将允许脂质修饰药物被递送到它们，并且这种治疗潜力的大部分仍然未被探索。因此，确定调节气道上皮细胞花生四烯酸代谢的因素仍然是阐明花生四烯酸产物在气道功能中的作用和改变气道中类二十烷酸产生的基本目标。
Airway epithelial cells carry out their physiologic role in part by activating phospholipase-fatty acid oxygenation pathways. Recent discoveries include the facts that (a) airway epithelial cells contain abundant stores of fatty acid substrates, including arachidonic acid, for oxygenation,(b) the cells release arachidonic acid upon activation of specific phospholipases,(c) the cells contain novel cyclooxygenases and lipoxygenases at high levels relative to other cell types, and (d) some of the arachidonate metabolites have potent biologic effects on airway end organs such as smooth muscle, nerves, mucus glands, and epithelial cells themselves. Studies of arachidonate metabolism in airway epithelial cells have often been done on a heterogeneous cell population of basal, ciliated, and goblet cells, so information on individual cell types and alterations during cellular differentiation is still poorly defined. Potential cell-cell interaction via transcellular synthesis of eicosanoids also requires further study. Each of these aims would be aided by the use of cultured airway epithelial cells, but the culture system has proven problematic in preserving the oxygenation phenotype of the original tissue. The same access of the epithelial cells to inhaled agents will permit lipid-modifying drugs to be delivered to them, and much of this therapeutic potential is still unexplored. Therefore, determining the factors that regulate arachidonic acid metabolism in airway epithelial cells is still a fundamental goal for unraveling the role of arachidonate products in airway function and for altering eicosanoid production in the airway.