Morphine-induced macrophage apoptosis modulates migration of macrophages:: Use of in vitro model of urinary tract infection
Morphine-induced macrophage apoptosis modulates migration of macrophages:: Use of in vitro model of urinary tract infection
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DOI：
10.1089/089277902320913314
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发表时间：
2002-10-01
影响因子：
2.7
通讯作者：
Singhal, PC
中科院分区：
文献类型：
--
作者：
Malik, AA;Radhakrishnan, N;Singhal, PC
背景：吗啡有改变免疫功能的报道。吗啡诱导的巨噬细胞凋亡已被证明有助于阿片环境下免疫状态的改变。研究吗啡诱导巨噬细胞凋亡对巨噬细胞迁移的影响。因为尿路感染（UTI）是引起炎症反应的最常见感染之一；即中性粒细胞和单核细胞向感染部位的迁移，我们使用体外尿路感染模型来验证我们的假设。材料和方法：我们进行了体内和体外研究。对FVB/N型小鼠进行短时（3次，24小时）和长时间（11次，96小时）吗啡治疗，并分离骨髓细胞。此外，通过热处理制备凋亡的巨噬细胞。为了模拟UTI的体外模型，使用大肠杆菌激活的小管细胞（TC）条件培养基，其中含有转化生长因子- β (tgf - β)和巨噬细胞-单核细胞化学引诱蛋白-1 (MCP-1)，在改良的Boyden室中测试巨噬细胞通过过滤器的迁移。此外，在对照组和吗啡治疗状态下，巨噬细胞向腹腔的迁移情况也被评估。研究了吗啡对小鼠巨噬细胞和骨髓细胞凋亡及迁移的影响。结果：吗啡不仅能促进骨髓细胞凋亡（20%），还能抑制骨髓细胞跨滤膜迁移。对照细胞凋亡最小，但迁移较大。同样，热处理（凋亡）细胞表现出最小的迁移。在腹腔巨噬细胞研究中，吗啡治疗延缓了巨噬细胞的迁移。结论：吗啡对巨噬细胞的体内外迁移均有抑制作用。巨噬细胞的这种减弱的迁移似乎是继发于吗啡的凋亡作用。
Background: Morphine has been reported to alter immune function. Morphine-induced macrophage apoptosis has been shown to contribute to altered immune status in an opiate milieu. We studied the effect of morphine-induced macrophage apoptosis on the migration of macrophages. Because urinary tract infection (UTI) is one of the commonest infections to evoke an inflammatory response; i.e., migration of neutrophils and monocytes to the site of infection, we used an in vitro model of UTI to test our hypothesis.Materials and Methods: We carried out both in vivo and in vitro studies. Mice of the FVB/N strain were treated with morphine for short (three doses, 24 hours) and long (11 doses, 96 hours) durations, and their bone marrow cells were isolated. In addition, apoptotic macrophages were prepared by heat treatment. To simulate the in vitro model of UTI, E. coli-activated tubular cell (TC )-conditioned medium containing transforming growth factor-beta (TGF-beta) and macrophage-monocyte chemoattractant protein-1 (MCP-1) was used to test migration of macrophages across a filter in a modified Boyden chamber. In addition, migration of macrophages into the peritoneal cavity was evaluated in both control and morphine-treated states. The effect of morphine on apoptosis as well as migration was studied in murine macrophages and bone marrow cells.Results: Morphine not only promoted apoptosis of bone marrow cells (20% apoptotic cells) but also inhibited their migration across the filter. Control cells showed minimal apoptosis but displayed greater migration. Similarly, heat-treated (apoptotic) cells showed minimal migration. In peritoneal macrophage studies, morphine treatment retarded migration.Conclusion: Morphine inhibits macrophage migration both in vivo and in vitro. This attenuated transmigration of macrophages seems to be secondary to the apoptotic effect of morphine.