Mast Cells Are an Essential Component of Human Radiation Proctitis and Contribute to Experimental Colorectal Damage in Mice
Mast Cells Are an Essential Component of Human Radiation Proctitis and Contribute to Experimental Colorectal Damage in Mice
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DOI：
10.1016/j.ajpath.2010.10.003
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发表时间：
2011-02-01
影响因子：
6
通讯作者：
Francois, Agnes
中科院分区：
文献类型：
--
作者：
Blirando, Karl;Milliat, Fabien;Francois, Agnes
放射性直肠炎的特点是粘膜炎症，随后是不良的慢性组织重塑，并与大量发病率和死亡率相关。肥大细胞增生与病理性组织重塑和纤维化等疾病有关。接受放射治疗的患者直肠组织显示肥大细胞增生和活化，提示这些细胞在放射诱导的后遗症的发展中起作用。为了研究肥大细胞在辐射损伤中的作用，我们在肥大细胞缺陷（W-sh/W-sh）小鼠模型中诱导实验性放射性直肠炎。将W-sh/W-sh和野生型小鼠的结肠和直肠分别置于27 gy单剂量照射下，分别于2周和14周后进行研究。经辐照的啮齿动物直肠显示肥大细胞增生。W-sh/W-sh小鼠发生的急性和慢性直肠辐射损伤比对照组小鼠少。组织保护与辐射暴露后立即增加的组织中性粒细胞内流和几种炎症介质的表达有关。肥大细胞乳糜酶、胰蛋白酶和组胺可使人固有肌层平滑肌细胞转变为迁移/增殖和促炎表型。这些数据表明，肥大细胞对急性和慢性放射性直肠炎都有有害影响，可能是通过限制急性组织中性粒细胞内流和支持平滑肌细胞的表型取向，从而使它们积极参与辐射诱导的炎症过程和直肠壁营养不良。（中华病理学杂志，2011,178:640-651;DOI: 10.1016/ j.j ajpath.2010.10.003）
Radiation proctitis is characterized by mucosal inflammation followed by adverse chronic tissue remodeling and is associated with substantial morbidity and mortality. Mast cell hyperplasia has been associated with diseases characterized by pathological tissue remodeling and fibrosis. Rectal tissue from patients treated with radiotherapy shows mast cell hyperplasia and activation, suggesting that these cells play a role in the development of radiation-induced sequelae. To investigate the role of mast cells in radiation damage, experimental radiation proctitis was induced in a mast cell-deficient (W-sh/W-sh) mouse model. The colon and rectum of W-sh/W-sh and wild-type mice were exposed to 27-Gy single-dose irradiation and studied after 2 and 14 weeks. Irradiated rodent rectum showed mast cell hyperplasia. W-sh/W-sh mice developed less acute and chronic rectal radiation damage than their control littermates. Tissue protection was associated with increased tissue neutrophil influx and expression of several inflammatory mediators immediately after radiation exposure. It was further demonstrated that mast cell chymase, tryptase, and histamine could change human muscularis propria smooth muscle cells into a migrating/proliferating and proinflammatory phenotype. These data show that mast cells have deleterious effects on both acute and chronic radiation proctitis, possibly by limiting acute tissue neutrophil influx and by favoring phenotypic orientation of smooth muscle cells, thus making them active participants in the radiation-induced inflammatory process and dystrophy of the rectal wall. (Am J Pathol 2011, 178:640-651; DOI: 10.1016/j.ajpath.2010.10.003)