Heiskanen K M, Naarala J, Savolainen K M
National Public Health Institute, Department of Toxicology, Kuopio, Finland.
Toxicology. 1995 Jun 26;100(1-3):195-202. doi: 10.1016/0300-483x(95)03090-3.
Human leukocytes were exposed to N-(5-vinyl-1,3-thiazolidin-2-ylidene)phenylamine (5-VTPA), a postulated impurity in the case oils that caused the Spanish Toxic Oil Syndrome in 1981. Changes induced by 5-VTPA alone and together with a chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP), a tumor promoter, phorbol myristate acetate (PMA), or a synthetic diacylglycerol, dioctanoyl-s,n-glycerol (DiC8) in free intracellular calcium levels ([Ca2+]i) and in the induction of oxidative burst were measured. 5-VTPA elevated dose-dependently [Ca2+]i and induced the production of reactive oxygen metabolites in leukocytes. 5-VTPA also amplified FMLP-induced increase in [Ca2+]i, but was without an effect on FMLP-induced oxidative burst. On the contrary, 5-VTPA amplified dose-dependently PMA- and DiC8-induced respiratory burst. The present results indicate that 5-VTPA may interfere with transmembrane signalling in human leukocytes. 5-VTPA may elevate [Ca2+]i by acting directly on the membrane, or by acting through Ca(2+)-mobilizing receptors. Moreover, 5-VTPA also clearly amplified responses produced through protein kinase C stimulation. Thus, 5-VTPA may act on human leukocytes by affecting Ca(2+)-metabolism and the activity of protein kinase C.
人类白细胞暴露于N-(5-乙烯基-1,3-噻唑烷-2-亚基)苯胺(5-VTPA),这是一种推测存在于某些润滑油中的杂质,该杂质在1981年引发了西班牙有毒食用油综合征。研究了单独的5-VTPA以及它与趋化肽甲酰甲硫氨酰亮氨酰苯丙氨酸(FMLP,一种肿瘤促进剂)、佛波酯肉豆蔻酸乙酸酯(PMA)或合成二酰甘油二辛酰-s,n-甘油(DiC8)共同作用时,对细胞内游离钙水平([Ca2+]i)以及氧化爆发诱导的影响。5-VTPA剂量依赖性地升高[Ca2+]i,并诱导白细胞中产生活性氧代谢产物。5-VTPA还增强了FMLP诱导的[Ca2+]i升高,但对FMLP诱导 的氧化爆发没有影响。相反,5-VTPA剂量依赖性地增强了PMA和DiC8诱导的呼吸爆发。目前的结果表明,5-VTPA可能干扰人类白细胞中的跨膜信号传导。5-VTPA可能通过直接作用于细胞膜或通过钙动员受体来升高[Ca2+]i。此外,5-VTPA还明显增强了通过蛋白激酶C刺激产生的反应。因此,5-VTPA可能通过影响钙代谢和蛋白激酶C的活性来作用于人类白细胞。