Leukotriene C4 and D4 contract rat glomerular mesangial cells.
Leukotriene C4 and D4 contract rat glomerular mesangial cells.
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白三烯 C4 和 D4 收缩大鼠肾小球系膜细胞。
DOI：
10.1038/ki.1986.217
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发表时间：
1986
影响因子：
19.6
通讯作者：
Dunn,MJ
中科院分区：
文献类型：
--
作者：
Simonson,MS;Dunn,MJ
白三烯C4和D4收缩大鼠肾小球系膜细胞。硫肽白三烯 LTC4 和 LTD4 在肾脏中具有血管收缩作用，可降低肾血流量和肾小球滤过率。作为调节肾小球滤过率的一种机制，系膜细胞收缩可能会减少毛细血管表面积，从而降低超滤系数。使用图像分析显微镜量化细胞形态的变化，我们发现LTC4和LTD4（1×10-12M至1×10-6M）减少了培养的大鼠肾小球系膜细胞的横截面积。对 LTC4 和 LTD4(10-6M) 的反应，以反应细胞的百分比（30% 至 35%）、横截面积最大减少（25% 至 32%）和时程来衡量，与血管紧张素 II (10-6M) 相同。 LTD4 诱导的收缩被 LTD4 受体拮抗剂 (4R,5S,6Z-nor-LTD1) 减弱。此外，用秋水仙碱预孵育可防止 LTC4 诱导的收缩。白三烯 B4 是一种非硫肽白三烯，可刺激趋化性和化学运动，其激动剂活性可忽略不计。与在玻璃或聚苯乙烯上培养的细胞（35% 的细胞响应）相比，在粘附性较低的聚四氟乙烯膜上培养的系膜细胞对 LTD4 的响应更灵敏（62% 的细胞响应）。系膜细胞收缩不仅仅是细胞损伤导致的形状变化，因为乳酸脱氢酶释放没有记录细胞损伤，并且 LTC4 也没有抑制系膜细胞的增殖。此外，收缩与细胞大小无关。由于白三烯会刺激其他细胞中的环氧合酶产物，因此我们检查了硫肽白三烯刺激前列腺素和血栓素合成的能力。 LTC4和LTD4不刺激PGE2的形成，PGE2是大鼠系膜细胞的主要环氧合酶产物。尽管 LTC4（而非 LTD4）刺激少量血栓素合成，但血栓素合成酶抑制剂 (UK-38485) 和受体拮抗剂 (EP-092) 不会改变白三烯介导的收缩。暴露于 LTC4 和 LTD4 的肾小球系膜细胞的收缩可能导致某些类型的肾小球损伤中超滤系数的降低。
Leukotriene C4and D4contract rat glomerular mesangial cells. The sulfidopeptide leukotrienes, LTC4and LTD4, have vasoconstrictor effects in the kidney, reducing both renal blood flow and the glomerular filtration rate. As one mechanism regulating the glomerular filtration rate, mesangial cell contraction may reduce the capillary surface area, thereby lowering the ultrafiltration coefficient. Using image analysis microscopy to quantify changes in cell morphology, we found that LTC4and LTD4(1×10-12Mto 1×10-6M) reduced the cross–sectional area of cultured mesangial cells from rat glomeruli. The response to LTC4and LTD4(10-6M), as measured by the percentage of responding cells (30 to 35%), the maximum decrease in cross–sectional area (25 to 32%), and the time course was identical to that for angiotensin II (10-6M). The contraction induced by LTD4was attenuated by an LTD4receptor antagonist (4R,5S,6Z-nor-LTD1). Also, preincubation with colchicine prevented LTC4-induced contraction. Leukotriene B4, a non-sulfidopeptide leukotriene that stimulates chemotaxis and chemo-kinesis, had negligible agonist activity. Mesangial cells cultured on less adhesive teflon membranes were more responsive to LTD4(62% of cells responded) than cells cultured on glass or polystyrene (35% of cells responded). Mesangial cell contraction was not merely a shape–change as a result of cell damage, since cellular injury was not documented by lactate dehydrogenase release and proliferation of mesangial cells was not retarded by LTC4. Furthermore, the contraction was independent of cell size. Because leukotrienes stimulate cyclooxygenase products in other cells, we examined the ability of the sulfidopeptide leukotrienes to stimulate prostaglandin and thromboxane synthesis. LTC4and LTD4did not stimulate PGE2formation, the major cyclooxygenase product of rat mesangial cells. Although LTC4, but not LTD4, stimulated a small amount of thromboxane synthesis, a thromboxane synthetase inhibitor (UK-38485) and a receptor antagonist (EP-092) did not alter leukotriene-mediated contraction. The contraction of mesangial cells exposed to LTC4and LTD4may contribute to the reduction in the ultrafiltration coefficient seen in some types of glomerular injury.