Modulation of the production of reactive oxygen species by pre-activated neutrophils by aminoadamantane derivatives
Modulation of the production of reactive oxygen species by pre-activated neutrophils by aminoadamantane derivatives
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DOI：
10.1016/s0006-2952(98)00024-0
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发表时间：
1998-07-01
影响因子：
5.8
通讯作者：
Elstner, EF
中科院分区：
文献类型：
--
作者：
Albrecht-Goepfert, E;Schempp, H;Elstner, EF
氨金刚烷衍生物(AAD)，如金刚烷胺或美金刚，已被用于治疗Morbus Parkinson和Morbus阿尔茨海默病。在这篇通讯中，我们报道了AAD的免疫调节活性。酵母多糖-，N-甲酰甲硫基亮氨酰苯丙氨酸或实验性钙离子载体(A 231879)预激活的中性粒细胞的鲁米诺依赖的化学发光在亚微摩尔浓度下被强烈增强，当浓度大于0.1mM时被抑制。与上述其他激活剂一样，phorbol-12-myristate-acetate(PMA)-preactivated细胞的光发射不会被更高的浓度进一步刺激，而是被抑制。α-酮基-甲硫基丁酸酯(KMB)生成乙烯作为NADPH-氧化酶(“呼吸爆发”)产生OH型活性氧物种的指示剂，被AAD促进，并被超氧化物歧化酶完全抑制。相反，1-氨基-环丙基-1-羧酸(ACC)作为脱颗粒后髓过氧化物酶反应的相对特异性指示剂的乙烯释放不受AAD的影响。正如几个模型反应所证明的那样，AAD本身并不作为活性氧物种的清除剂或猝灭剂，如超氧化物、OH-自由基、过氧化氢或次氯酸盐。总之，这些结果表明，亚微摩尔浓度的AAD上调了呼吸爆发，但显然不能促进刺激前多形核白细胞的脱颗粒。然而，当AAD浓度较高时，呼吸爆发和脱颗粒都会受到抑制。这些影响也可以在完整的血液样本中显示出来。Biochem Pharmacol 56；1：141-152,1998。(C)1998年爱思唯尔科学公司。
Aminoadamantane derivatives (AAD) such as amantadine or memantine have been used for the treatment of Morbus Parkinson and Morbus Alzheimer. In this communication, we report on the immunomodulatory activities of AAD. Luminol-dependent chemiluminescence of zymosan-, N-formylmethionylleucylphenylalanine(FMLP) or experimental Ca2+-ionophore(A 231879)-preactivated polymorphonuclear leukocytes (PMN) was strongly enhanced by submicromolar concentrations of AAD and inhibited at higher concentrations than 0.1 mM. Light emission by phorbol-12-myristate-acetate(PMA)-preactivated cells was not further stimulated but inhibited by the elevated concentrations, just as with the other, above-mentioned activators. Ethylene formation from alpha-keto-methylthiobutyrate (KMB) as an indicator for production of OH.-type reactive oxygen species by the NADPH-oxidase ("respiratory burst") was augmented by AAD and completely inhibited by superoxide dismutase. In contrast, ethylene release from 1-amino-cyclopropyl-1-carboxylic acid (ACC) as relatively specific indicator for the myeloperoxidase reaction after degranulation was not influenced by AAD. As documented by several model reactions, AAD per se did nor act as scavengers or quenchers of activated oxygen species such as superoxide, OH.-radical, hydrogen peroxide or hypochlorite. Altogether, these results suggest that submicromolar concentrations of AAD upregulate the respiratory burst, but apparently not the degranulation of prestimulated polymorphonuclear leukocytes. At higher concentrations of AAD, both respiratory burst and degranulation are inhibited, however. These effects can also be shown in complete blood samples. BIOCHEM PHARMACOL 56;1:141-152, 1998. (C) 1998 Elsevier Science Inc.