Duchiron C, Reynaud S, Deschaux P
Laboratory of General and Comparative Immunophysiology, UER of Sciences, 123, av. Albert Thomas, 87060 Limoges, France.
Aquat Toxicol. 2002 Jan;56(2):81-91. doi: 10.1016/s0166-445x(01)00193-x.
We studied the in vitro effects of the insecticide lindane (2.5-50 microM) on macrophage activating factor (MAF) production by the peripheral blood leukocytes (PBLs) in rainbow trout. The MAF production induced by the mitogens concanavalin A (ConA) and phorbol-12-myristate-13-acetate (PMA) was not modified by lindane pre-treatment. But lindane alone (2.5-25 microM) stimulated the secretion of MAF by PBLs. Intracellular calcium levels ([Ca2+]i) was measured over 6 min by spectrofluorimetry using Indo-1/AM as fluorescent probe. Lindane (25-100 microM) significantly increased the [Ca2+]i in PBLs, but had no effect on calcium at the dose that caused MAF secretion. Moreover, the effect of lindane on MAF production was potentiated by the inhibitor of phosphodiesterase, isobutylmethylxanthin (IBMX). Lindane also directly increased adenosine monophosphate cyclic (cAMP) in PBLs over the same concentration range that it stimulated MAF production by PBLs. Taken together, these results suggest that lindane increase MAF production by acting on intracellular cAMP concentrations. Moreover, the capacity of this insecticide to act on the [Ca2+]i or on the intracellular concentrations of cAMP according to the dose used could possibly explain its contradictory effects earlier observed on immunity.
我们研究了杀虫剂林丹（2.5 - 50微摩尔）对虹鳟鱼外周血白细胞（PBLs）产生巨噬细胞激活因子（MAF）的体外作用。用促细胞分裂剂刀豆球蛋白A（ConA）和佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）诱导产生的MAF，经林丹预处理后未发生改变。但单独使用林丹（2.5 - 25微摩尔）可刺激PBLs分泌MAF。使用吲哚-1/AM作为荧光探针，通过荧光分光光度法在6分钟内测量细胞内钙水平（[Ca2+]i）。林丹（25 - 100微摩尔）显著增加了PBLs中的[Ca2+]i，但在引起MAF分泌的剂量下对钙没有影响。此外，磷酸二酯酶抑制剂异丁基甲基黄嘌呤（IBMX）增强了林丹对MAF产生的作用。在刺激PBLs产生MAF的相同浓度范围内，林丹还直接增加了PBLs中的环磷酸腺苷（cAMP）。综上所述，这些结果表明林丹通过作用于细胞内cAMP浓度来增加MAF的产生。此外，这种杀虫剂根据所用剂量作用于[Ca2+]i或细胞内cAMP浓度的能力，可能解释了其早期观察到的对免疫的矛盾作用。
