Klockmann M T, Jahn H U, Hippenstiel S, Krämer H J, Suttorp N
Department of Internal Medicine, Justus-Liebig-University of Giessen, Germany.
J Cell Physiol. 1998 Jun;175(3):268-75. doi: 10.1002/(SICI)1097-4652(199806)175:3<268::AID-JCP4>3.0.CO;2-M.
Airway epithelial cells (AEC) play an active role in the regulation of inflammatory airway disease. In the present study we analyzed the interaction of AEC with polymorphonuclear leukocytes (PMN) in coincubation with respect to their arachidonic acid (AA) metabolism using reversed phase-HPLC and post-HPLC-ELISA. Primary cultures of porcine AEC released predominantly PGE2, PGF2a, and 15-hydroxyeicosatetraenoic acid (15-HETE), whereas the major human PMN-derived AA metabolite was the chemotactic factor leukotriene B4 (LTB4). In AEC-PMN cocultures stimulated with the calcium ionophore A23187, PMN-related 5-lipoxygenase products were decreased by 45%. This reduction in LTB4 formation in the presence of AEC was mainly due to PGE2 generated by the epithelial cells, whereas 15-HETE made a minor contribution. Most of the effect was inhibited by AEC pretreatment with acetylsalicylic acid and restored by addition of equivalent amounts of exogenous PGE2. LTB4 degradation was not enhanced in PMN-AEC coincubations. Moreover, reduction of LTB4 formation in this system did not require an intimate cell-to-cell contact as shown by studies involving filter membranes for PMN-AEC separation. Superoxide anion concentrations were also decreased in PMN-AEC coincubations; this effect, however, was unrelated to PGE2 for quantitative reasons and was probably due to O2- degradation by epithelial cells. In summary, epithelially derived PGE2 is the major mediator in the coincubation of porcine AEC and human PMN that downregulates neutrophil responses by activating receptors on the neutrophil. A minor contributor in this course of PMN-AEC interaction may be the 15-HETE transcellular pathway. Overall, airway epithelium appears to play an antiinflammatory role by damping the proinflammatory potential of neutrophils.
气道上皮细胞（AEC）在炎症性气道疾病的调节中发挥着积极作用。在本研究中，我们使用反相高效液相色谱法（reversed phase-HPLC）和高效液相色谱后酶联免疫吸附测定法（post-HPLC-ELISA）分析了AEC与多形核白细胞（PMN）共孵育时它们在花生四烯酸（AA）代谢方面的相互作用。猪AEC原代培养物主要释放前列腺素E2（PGE2）、前列腺素F2α（PGF2α）和15-羟基二十碳四烯酸（15-HETE），而人PMN衍生的主要AA代谢产物是趋化因子白三烯B4（LTB4）。在用钙离子载体A23187刺激的AEC-PMN共培养物中，与PMN相关的5-脂氧合酶产物减少了45%。在存在AEC的情况下，LTB4生成的这种减少主要是由于上皮细胞产生的PGE2，而15-HETE的作用较小。大部分作用被乙酰水杨酸预处理的AEC抑制，并通过添加等量的外源性PGE2恢复。在PMN-AEC共孵育中，LTB4的降解没有增强。此外，如涉及用于PMN-AEC分离的滤膜的研究所表明的，该系统中LTB4生成的减少不需要紧密的细胞间接触。在PMN-AEC共孵育中，超氧阴离子浓度也降低；然而，由于定量原因，这种作用与PGE2无关，可能是由于上皮细胞对O2-的降解。总之，上皮来源的PGE2是猪AEC和人PMN共孵育中的主要介质，它通过激活中性粒细胞上的受体来下调中性粒细胞反应。在PMN-AEC相互作用的这个过程中，一个较小的贡献者可能是15-HETE跨细胞途径。总体而言，气道上皮似乎通过抑制中性粒细胞的促炎潜能发挥抗炎作用。
