Woodward D F, Gary R K, Spada C S, Hawley S B, Nieves A L
Allergan, Inc., Department of Biology, CA 92715.
J Lipid Mediat. 1989 Jan-Feb;1(1):63-73.
The time course of extravascular albumin accumulation responses elicited by the leukotrienes LTC4, LTD4, LTE4, and histamine in the skin were compared in the conscious guinea pig. During the initial 15-min period, comparison of the dose-response curves revealed that histamine produced a much larger increase in extravascular albumin content than any of the leukotrienes. One hour after intradermal injection and at subsequent time intervals, the response to LTD4 had increased in magnitude so that it equaled the response produced by histamine. This was apparent from comparison of the time courses of extravascular albumin accumulation for intermediate doses of LTD4 and histamine and also from comparison of dose-response relationships at 4 h post intradermal injection. In contrast to LTD4, the magnitude of the microvascular permeability responses to LTC4 and LTE4 remained relatively small even over an extended time scale. Although histamine produced a large initial response, this also remained essentially unchanged over a 4-h period. It appears that LTD4 may produce a unique, time-dependent cutaneous microvascular permeability response and measurements over 15-30-min periods may underestimate its activity as a vasopermeability factor. The time-dependent effects of LTD4 on albumin extravasation cannot be ascribed to leukocyte infiltration into the skin since LTC4, LTD4, and LTE4 were entirely without effect in this regard.
在清醒的豚鼠中比较了白三烯LTC4、LTD4、LTE4和组胺在皮肤中引起的血管外白蛋白积聚反应的时间进程。在最初的15分钟内，剂量反应曲线的比较显示，组胺引起的血管外白蛋白含量增加比任何一种白三烯都大得多。皮内注射1小时后及随后的时间间隔，对LTD4的反应强度增加，以至于与组胺产生的反应相当。这从LTD4和组胺中等剂量的血管外白蛋白积聚时间进程比较以及皮内注射4小时后的剂量反应关系比较中可以明显看出。与LTD4相反，即使在较长时间内，对LTC4和LTE4的微血管通透性反应强度仍然相对较小。虽然组胺产生了较大的初始反应，但在4小时内也基本保持不变。似乎LTD4可能产生独特的、时间依赖性的皮肤微血管通透性反应，在15 - 30分钟内进行测量可能会低估其作为血管通透性因子的活性。LTD4对白蛋白外渗的时间依赖性影响不能归因于白细胞浸润到皮肤中，因为LTC4、LTD4和LTE4在这方面完全没有作用。
