Meier H L, Warner J, MacGlashan D W
Research Institute of Chemical Defense, Aberdeen Proving Grounds, MD 21010, USA.
Int J Immunopharmacol. 1995 Apr;17(4):283-9. doi: 10.1016/0192-0561(95)00005-m.
Previous studies noted that the serine esterase inhibitor, soman, could induce histamine release from human basophils. To investigate the mechanisms by which soman causes histamine release (a preformed mediator), we also examined its ability to induce leukotriene release (a newly synthesized mediator) from basophils. We found that no leukotriene release followed activation with soman, while histamine release was usually greater than 70%. In addition, soman and diisopropyl-fluorophosphate were found actively to suppress low level spontaneous leukotriene release as well as ongoing leukotriene release induced by anti-IgE antibody. Soman (0.3 mM) was able to stop leukotriene release as rapidly as the calcium chelator, EDTA. In a series of control experiments, it was noted that soman did not influence the metabolism of LTC4 to LTD4 or LTE4 (for which little metabolism occurred), eliminating the possibility that reduced LTC4 release could have resulted from its enhanced metabolism. Therefore, using one compound (soman), basophils could be simultaneously activated to degranulate while having the pathway leading to leukotriene release actively suppressed. These results provide further evidence that histamine and leukotriene release are independent pathways resulting from the activation of basophils.
以往的研究指出，丝氨酸酯酶抑制剂梭曼可诱导人嗜碱性粒细胞释放组胺。为了研究梭曼引起组胺释放（一种预先形成的介质）的机制，我们还检测了其诱导嗜碱性粒细胞释放白三烯（一种新合成的介质）的能力。我们发现，用梭曼激活后不会有白三烯释放，而组胺释放通常大于70%。此外，还发现梭曼和二异丙基氟磷酸可有效抑制低水平的自发性白三烯释放以及抗IgE抗体诱导的持续性白三烯释放。梭曼（0.3 mM）能够像钙螯合剂乙二胺四乙酸一样迅速地阻止白三烯释放。在一系列对照实验中，注意到梭曼不影响LTC4向LTD4或LTE4的代谢（几乎没有发生代谢），排除了LTC4释放减少可能是由于其代谢增强所致的可能性。因此，使用一种化合物（梭曼），可同时激活嗜碱性粒细胞使其脱颗粒，同时使导致白三烯释放的途径受到有效抑制。这些结果进一步证明组胺和白三烯释放是嗜碱性粒细胞激活产生的独立途径。
