Transcellular metabolism of neutrophil-derived leukotriene A4 by human platelets. A potential cellular source of leukotriene C4.
Transcellular metabolism of neutrophil-derived leukotriene A4 by human platelets. A potential cellular source of leukotriene C4.
复制标题
DOI：
10.1016/s0021-9258(19)57375-6
复制
发表时间：
1988-01
期刊：
影响因子：
--
通讯作者：
Jacques A. MacloufS;R. C. Murphy
中科院分区：
文献类型：
--
作者：
Jacques A. MacloufS;R. C. Murphy
已发现人血小板能够以相当有效的方式将白三烯 (LT) A4 转化为白三烯 C4。 LTC4 通过高效液相色谱、紫外分光光度法、标记前体的使用、豚鼠回肠生物测定和酶免疫测定的组合进行表征。研究发现，LTA4 代谢具有底物依赖性、时间依赖性，并且与血小板浓度成正比，即使在亚生理水平或超生理水平（0.0019-1 X 10(9) 血小板/ml）也是如此。在还原型谷胱甘肽存在或不存在的情况下，单独的血浆以及静息或活化血小板的上清液均未发现催化LTC4的产生。这些数据表明血小板含有 LTC4 生物合成特异性的谷胱甘肽 S-转移酶。当 LTA4 在白蛋白存在下与血小板一起孵育时，LTC4 的形成大大增强。低浓度的白蛋白 (2-4 g/L) 可稳定 LTA4，使其在孵育 1 小时后可检测到血小板转化为 LTC4。测试了 LTA4 在中性粒细胞和血小板之间可能的细胞间转移。在血小板存在的情况下，嗜中性粒细胞产生 LTC4 的能力大大增强。此外，用钙离子载体刺激的中性粒细胞上清液含有短寿命的酸不稳定物质，该物质被血小板转化为LTC4。当用[35S]半胱氨酸预先标记血小板以允许细胞内合成[35S]谷胱甘肽时，用钙离子载体攻击的两种细胞类型的共孵育导致[35S]LTC4的产生。这些数据表明血小板可以从中性粒细胞衍生的LTA4产生大量LTC4。他们还表明，这种相互作用可能在体内发生，并且血小板可能对生物活性 LTC4 的产生做出重要贡献。
Transformation of leukotriene (LT) A4 into leukotriene C4 has been found to be carried out by human platelets in a rather efficient manner. LTC4 was characterized by a combination of high performance liquid chromatography, UV spectrophotometry, use of labeled precursor, guinea pig ileum bioassay, and enzyme immunoassay. LTA4 metabolism was found to be substrate-dependent, time-dependent, and proportional to platelet concentration even at sub- or supraphysiological levels (0.0019-1 X 10(9) platelets/ml). Neither plasma alone nor the supernatant of resting or activated platelets was found to catalyze the production of LTC4 in the presence or in the absence of reduced glutathione. These data suggest that platelets contain a glutathione S-transferase specific for LTC4 biosynthesis. The formation of LTC4 was greatly enhanced when LTA4 was incubated with platelets in the presence of albumin. Low concentrations of albumin (2-4 g/liter) stabilized LTA4 to an extent that conversion into LTC4 by the platelets could be detected after 1 h of incubation. The possible intercellular transfer of LTA4 between neutrophils and platelets was tested. The production of LTC4 by neutrophils was greatly enhanced in the presence of platelets. Furthermore, the supernatant of neutrophils stimulated with the calcium ionophore contained a short-lived acid-labile substance which was converted by the platelets into LTC4. When platelets were prelabeled with [35S]cysteine to allow intracellular synthesis of [35S]glutathione, the coincubation of both cell types challenged with the calcium ionophore resulted in the production of [35S] LTC4. These data indicate that platelets can produce large amounts of LTC4 from neutrophil-derived LTA4. They also suggest that such interactions may occur in vivo and that platelets could be an important contribution to the generation of the biologically active LTC4.