LIPOXIN A(4) MODULATES TRANSMIGRATION OF HUMAN NEUTROPHILS ACROSS INTESTINAL EPITHELIAL MONOLAYERS
LIPOXIN A(4) MODULATES TRANSMIGRATION OF HUMAN NEUTROPHILS ACROSS INTESTINAL EPITHELIAL MONOLAYERS
复制标题
DOI：
10.1172/jci116601
复制
发表时间：
1993-07-01
影响因子：
15.9
通讯作者：
MADARA, JL
中科院分区：
文献类型：
--
作者：
COLGAN, SP;SERHAN, CN;MADARA, JL
中性粒细胞 (PMN) 穿过肠上皮屏障迁移，例如在许多疾病状态下发生的情况，导致上皮屏障发生改变。在这里，我们研究了脂氧素 A4 (LXA4)（一种具有反调节炎症作用的类二十烷酸）对 PMN 在人肠上皮细胞系 T84 培养单层中迁移的影响。在顶端到基底外侧方向和基底外侧到顶端方向评估 PMN 的跨上皮迁移。在从顶端到基底外侧的方向上，PMN 预暴露于 LXA4（10 nM，15 分钟）刺激 PMN 的跨上皮迁移增加 87 +/- 5%（通过 PMN 髓过氧化物酶测定确定）。 LXA4 引起的对轮回的影响在整个 2 小时测定期间都存在，并且根据跨上皮阻力的测量判断，并不是继发于 LXA4 对上皮单层完整性的影响。 PMN 从基底外侧到基底外侧方向的迁移受到 LXA4 的调节，其时间和浓度依赖性与从基底外侧到基底外侧方向的迁移具有相当的时间和浓度依赖性。 然而，观察到 LXA4 在两个相反方向上调节轮回的方式存在质的差异。在基底外侧至心尖方向，PMN 预先暴露于 LXA4（10 nM，15 分钟）可使 PMN 跨上皮迁移减少 33 +/- 4%。结构功能研究表明，LXA4 和 11-trans-LXA4（LXA4 效应的 50%）（但 LXB4 没有）抑制基底外侧到顶端的 PMN 迁移。 LXA4 的作用对环氧合酶抑制剂或特定白三烯生物合成不敏感，但对星形孢菌素（一种蛋白激酶 C 抑制剂）敏感。这些结果表明，中性粒细胞暴露于类二十烷酸后，中性粒细胞在上皮细胞上沿生理方向的迁移可能会发生质的不同。我们认为，PMN 在这个特定解剖位置的保留可能在粘膜防御中发挥重要作用。
Neutrophil (PMN) migration across intestinal epithelial barriers, such as occurs in many disease states, results in modifications in epithelial barrier. Here, we investigated the impact of lipoxin A4 (LXA4), an eicosanoid with counterregulatory inflammatory roles, on PMN migration across cultured monolayers of the human intestinal epithelial cell line T84. Transepithelial migration of PMN was assessed in the apical-to-basolateral direction and in the basolateral-to-apical direction. In the apical-to-basolateral direction, preexposure of PMN to LXA4 (10 nM, 15 min) stimulated an 87 +/- 5% increase in transepithelial migration of PMN as determined by a PMN myeloperoxidase assay. The LXA4-elicited effect on transmigration was present throughout the 2-h assay period and was not secondary to LXA4 effects on epithelial monolayer integrity as judged by measurement of transepithelial resistance. PMN migration in the basolateral-to-apical direction was modulated by LXA4 with a comparable time- and concentration-dependence to that in the apical-to-basolateral direction. However, qualitative differences in how LXA4 Modulates transmigration in the two opposing directions were observed. In the basolateral-to-apical direction, preexposure of PMN to LXA4 (10 nM, 15 min) diminished PMN transepithelial migration by 33 +/- 4%. Structure-function studies revealed that LXA4 and 11-trans-LXA4 (50% of LXA4 effect), but not LXB4, inhibited basolateral-to-apical PMN transmigration. The action of LXA4 was not sensitive to inhibitors of cyclooxygenase or specific leukotriene biosynthesis, but was sensitive to staurosporine, a protein kinase C inhibitor. These results suggest that migration of PMN across epithelia in the physiological direction may be qualitatively different following PMN exposure to eicosanoids. We propose that such retention of PMN at this specific anatomic location may serve an important role in mucosal defense.