Simultaneous activation of granulocytes and extrathymic T cells in number and function by excessive administration of nonsteroidal anti-inflammatory drugs.
Simultaneous activation of granulocytes and extrathymic T cells in number and function by excessive administration of nonsteroidal anti-inflammatory drugs.
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DOI：
10.1006/cimm.1996.0282
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发表时间：
1996-11
影响因子：
4.3
通讯作者：
S. Yamamura;K. Arai;S. Toyabe;H. Takahashi;T. Abo
中科院分区：
文献类型：
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作者：
S. Yamamura;K. Arai;S. Toyabe;H. Takahashi;T. Abo
非甾体抗炎药（NSAID）有时会显示严重的副作用，如胃十二指肠粘膜损伤和肝脏功能障碍。虽然许多研究者都集中在某些类型的白细胞，一个全面的研究涉及所有类型的白细胞，特别是最近发现的胸腺外T细胞，仍然有待完成。当小鼠腹腔注射吲哚美辛（50或300 μ g/只）时，胸腺细胞数量减少，而各种外周器官中的MNC数量增加。MNC的增加主要是由于粒细胞和胸腺外T细胞数量的增加。反映胸腺萎缩，胸腺来源的T细胞分布在外周的比例下降。其他NSAID的使用显示，外周中观察到的粒细胞增多症是骨髓中粒单核细胞的选择性激活引起的。以Ca 2+内流、iNOSmRNA表达和自身反应性细胞毒性为指标的功能实验表明，粒细胞和胸腺外T细胞不仅在数量上而且在功能上都处于激活状态。由于粒细胞和胸腺外T细胞在过度活化时都成为针对自身组织或自身细胞的细胞毒性效应物，这些活化的白细胞可能与NSAID诱导的组织损伤的病因学密切相关（即，药物不良反应）。
Nonsteroidal anti-inflammatory drugs (NSAIDs) sometimes show serious side effects such as damage to the gastroduodenal mucosa and dysfunction of the liver. Although many investigators have focused on some types of leukocytes, a comprehensive study concerning all types of leukocytes, especially recently identified extrathymic T cells, remains to be done. When mice were treated with an intraperitoneal injection of indomethacin (50 or 300 microg/mouse), the number of thymocytes decreased while the number of MNC in various peripheral organs increased. This increase in MNC was due mainly to the increase in the numbers of granulocytes and extrathymic T cells. Reflecting thymic atrophy, the proportion of thymus-derived T cells distributed in the periphery decreased. The use of other NSAIDs revealed that granulocytosis seen in the periphery arose from a selective activation of myelomonocytic cells in the bone marrow. Some functional experiments using the Ca2+ influx, iNOS mRNA expression, and autoreactive cytotoxicity as indicators suggested that granulocytes and extrathymic T cells were in activated states not only in number but also in function. Since both granulocytes and extrathymic T cells become cytotoxic effectors against self-tissues or self-cells when overactivated, these activated leukocytes may be intimately related to the etiology of the tissue damage inducible by NSAIDs (i.e., adverse drug reaction).