2-乙基己酸对人多形核白细胞体外产生活性氧的影响。

Effects of 2-ethylhexanoic acid on the production of reactive oxygen species in human polymorphonuclear leukocytes in vitro.

作者信息

Pennanen S M, Heiskanen K M, Savolainen K M, Komulainen H

机构信息

Finnish Institute of Occupational Health, P.O. Box 93, FIN-70701, Kuopia, Finland.

出版信息

Toxicol Lett. 2000 Sep 30;117(1-2):79-84. doi: 10.1016/s0378-4274(00)00243-5.

DOI:10.1016/s0378-4274(00)00243-5

PMID:11033236

Abstract

2-Ethylhexanoic acid (2-EHA), is an industrial chemical and a toxic biotransformation product of the plasticizer di(2-ethylhexyl)phthalate. Its immunological effects are unknown. 2-EHA resembles structurally C18 fatty acids, which are known activators of respiratory burst in human polymorphonuclear leukocytes (PMNL). Therefore, we exposed PMNL to 2-EHA in vitro and measured the production of reactive oxygen species (ROS) and explored the associated cellular mechanisms. 2-EHA (10-2000 microM) inhibited dose-dependently formyl-methionyl-leucyl-phenylalanine (FMLP)-induced respiratory burst in PMNL. Moreover, 2-EHA decreased oxidative burst evoked by the protein kinase C (PKC) activators, phorbol myristate acetate (PMA) and dioctanoyl-s,n-glycerol (DIC(8)). 2-EHA affected neither the levels of free intracellular calcium nor inhibited PKC. The results indicate that 2-EHA inhibits activation of PMNL to produce ROS, i.e. has an immunosuppressive effect in vitro. The site of action in the PKC is after activation of this enzyme.

摘要

2-乙基己酸（2-EHA）是一种工业化学品，也是增塑剂邻苯二甲酸二（2-乙基己基）酯的有毒生物转化产物。其免疫效应尚不清楚。2-EHA在结构上类似于C18脂肪酸，而C18脂肪酸是已知的人类多形核白细胞（PMNL）呼吸爆发的激活剂。因此，我们在体外将PMNL暴露于2-EHA，并测量活性氧（ROS）的产生，同时探索相关的细胞机制。2-EHA（10 - 2000微摩尔）剂量依赖性地抑制了PMNL中N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）诱导的呼吸爆发。此外，2-EHA降低了蛋白激酶C（PKC）激活剂佛波酯（PMA）和二辛酰-s,n-甘油（DIC(8)）诱发的氧化爆发。2-EHA既不影响细胞内游离钙水平，也不抑制PKC。结果表明，2-EHA抑制PMNL产生ROS的激活，即在体外具有免疫抑制作用。其在PKC中的作用位点是在该酶激活之后。