Development of peritoneal adhesions in macrophage depleted mice
Development of peritoneal adhesions in macrophage depleted mice
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DOI：
10.1016/j.jss.2005.08.026
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发表时间：
2006-04-01
影响因子：
2.2
通讯作者：
Cohen, DA
中科院分区：
文献类型：
--
作者：
Burnett, SH;Beus, BJ;Cohen, DA
背景我们提出了一种新的小鼠模型，使用巨噬细胞Fas诱导的细胞凋亡（黑手党）转基因小鼠表达的Fas-FKBP构建的小鼠c-fms启动子的控制下，腹膜粘连的研究。Mafia小鼠允许通过用合成二聚化剂AP 20187使Fas二聚化来消耗全身巨噬细胞。结果表明，当腹腔也暴露于刺激物时，Mafia小鼠中的巨噬细胞耗竭诱导腹膜粘连形成。Mafia小鼠模型为粘连形成和预防的研究提供了一种可重复的非手术方法。Mafia小鼠使用静脉内（i. v.）或腹膜内（i. p.）注射对照组包括模拟处理的Mafia小鼠以及AP 20187和模拟处理的野生型小鼠。治疗后7天，观察小鼠是否存在粘连。腹腔注射AP 20187后，76%的Mafia小鼠发生粘连，而模拟给药Mafia或野生型小鼠均未发生粘连，仅1只AP 20187给药野生型小鼠（5.8%）发生轻度粘连。经AP 20187 i. v.给药的Mafia小鼠表现出与i. p.给药小鼠无显著差异的巨噬细胞耗竭，但未发生粘连。相比之下，当稀释剂也注射到腹腔时，用AP 20187静脉注射处理的Mafia小鼠发生粘连，而单独的i.p稀释剂没有影响。在转基因Mafia小鼠中，巨噬细胞耗竭与腹膜刺激物结合导致腹膜粘连形成。巨噬细胞似乎在腹膜粘连的发展和/或修复中起保护作用。(C)2005年爱思唯尔公司All rights reserved.
Background. We present a new mouse model for the study of peritoneal adhesions using macrophage Fas-induced apoptosis (Mafia) transgenic mice expressing a Fas-FKBP construct under control of the murine c-fms promoter. Mafia mice allow systemic macrophage depletion by dimerization of Fas with a synthetic dimerizer, AP20187. Results demonstrate that macrophage depletion in Mafia mice induces peritoneal adhesion formation when the peritoneal cavity is also exposed to an irritant. The Mafia mouse model presents a reproducible, non-surgical approach for research in adhesion formation and prevention.Materials and methods. Mafia mice were treated with AP20187 using an intravenous (i.v.) or intraperitoneal (i.p.) injection. Control groups included mock-treated Mafia mice and both AP20187 and mock-treated wild type mice. Seven days after treatment, mice were observed for the presence of adhesions.Results. After i.p. injection with AP20187, 76% of Mafia mice developed adhesions whereas none of the mock-treated Mafia or wild-type mice developed adhesions, and only one AP20187-treated wild-type mouse (5.8%) developed a mild adhesion. Mafia mice treated with AP20187 i.v. exhibited macrophage depletion not significantly different than i.p. treated mice, but did not develop adhesions. In contrast, Mafia mice treated with AP20187 i.v. developed adhesions when diluent was also injected into the peritoneal cavity, whereas i.p diluent alone had no effect.Conclusion. Macrophage depletion, combined with a peritoneal irritant, results in peritoneal adhesion formation in transgenic Mafia mice. Macrophages appear to play a protective role in the development and/or repair of peritoneal adhesions. (C) 2005 Elsevier Inc. All rights reserved.