Adriamycin promotes macrophage dysfunction in mice
Adriamycin promotes macrophage dysfunction in mice
复制标题
DOI：
10.1016/j.freeradbiomed.2006.03.027
复制
发表时间：
2006-07-01
影响因子：
7.4
通讯作者：
Asmis, Lars M.
中科院分区：
文献类型：
--
作者：
Asmis, Reto;Qiao, Mu;Asmis, Lars M.
伤口愈合不良导致阿霉素化疗相关的发病率和死亡率。巨噬细胞是组织修复所必需的，巨噬细胞功能的丧失导致伤口愈合受损。我们最近表明阿霉素是培养的巨噬细胞中硫醇氧化和细胞损伤的有效诱导剂（FASEB J. 19：1866-1868; 2005）。在这里，我们测试的假设，阿霉素也促进体内氧化应激和巨噬细胞功能障碍。我们每周两次用低剂量的阿霉素（4 mg/kg）或用相同体积的盐水通过尾静脉注射治疗FVB小鼠，总共8次注射。阿霉素治疗的小鼠伤口愈合明显延迟。在阿霉素处理的小鼠中，驻留的腹腔巨噬细胞的数量减少了30%，并且响应于硫代乙酸盐刺激的巨噬细胞募集减少了46%。与从盐水注射小鼠分离的巨噬细胞相比，阿霉素处理小鼠巨噬细胞的LPS诱导的TNF α和IL-1 β分泌分别降低了28.7%和29.5%。从阿霉素处理的小鼠中分离的腹膜巨噬细胞也显示活性氧簇的形成增加和蛋白质-S-谷胱甘肽化增强。总之，我们的研究结果表明，低累积剂量的阿霉素足以促进体内持续的硫醇氧化应激和巨噬细胞功能障碍，并延迟组织修复，这表明巨噬细胞功能障碍有助于与阿霉素化疗相关的伤口愈合受损。(c)2006年爱思唯尔公司所有的战斗保留。
Impaired wound healing contributes to the morbidity and mortality associated with adriamycin chemotherapy. Macrophages are essential for tissue repair and loss of macrophage function leads to impaired wound healing. We recently showed that adriamycin is a potent inducer of thiol oxidation and cell injury in cultured macrophages (FASEB J. 19:1866-1868; 2005). Here we tested the hypothesis that adriamycin also promotes oxidative stress and macrophage dysfunction in vivo. We treated FVB mice twice a week either with low doses of adriamycin (4 mg/kg) or with the same volume of saline by tail vein injection for a total of 8 injections. Wound healing was significantly delayed in adriamycin-treated mice. The number of resident peritoneal macrophages was decreased by 30% and macrophage recruitment in response to thiogycolate stimulation was decreased by 46% in mice treated with adriamycin. LPS-induced TNF alpha and IL-1 beta secretion from macrophages of adriamycin-treated mice was decreased by 28.7 and 29.5%, respectively, compared to macrophages isolated from saline-injected mice. Peritoneal macrophages isolated from adriamycin-treated mice also showed increased formation of reactive oxygen species and enhanced protein-S-glutathionylation. In summary, our results show that low cumulative doses of adriamycin are sufficient both to promote sustained thiol oxidative stress and macrophage dysfunction in vivo and to delay tissue repair, suggesting that macrophage dysfunction contributes to impaired wound healing associated with adriamycin chemotherapy. (c) 2006 Elsevier Inc. All fights reserved.