Villus epithelial injury induced by infection with the nematode Nippostrongylus brasiliensis is associated with upregulation of granzyme B

Villus epithelial injury induced by infection with the nematode Nippostrongylus brasiliensis is associated with upregulation of granzyme B
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DOI:
10.1645/ge-265r
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发表时间:
2004-10-01
影响因子:
1.3
通讯作者:
Arizono, N
Arizono, N
中科院分区:
医学4区
文献类型:
--
作者:
Fujiwara, A;Kawai, Y;Arizono, N

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肠道寄生虫感染可诱导胸腺依赖性绒毛萎缩,但直接导致绒毛萎缩的效应机制尚不完全清楚。在本研究中,我们分析了感染巴西尼波圆线虫的裸胸大鼠及其幼崽euthyinic rnu/+大鼠的细胞毒因子或配体的表达。形态计量学分析显示,感染后10天,健忘型大鼠绒毛部分萎缩,健忘型大鼠绒毛部分萎缩,而两种动物均出现隐窝增生。空肠上皮逆转录聚合酶链反应分析表明,健康大鼠绒毛萎缩的发生与颗粒酶B转录物水平的增加呈正相关,而与Fas配体或肿瘤坏死因子- α的表达无关。感染后,健脾大鼠绒毛上皮和固有黏膜颗粒酶b免疫反应细胞数量明显增加。CD8(+)细胞数量无明显变化。总的来说,这些发现表明,在免疫功能正常的线虫感染的宿主小肠中,表达细胞毒性因子颗粒酶B的细胞数量显著增加。表达颗粒酶B的细胞类型及其在肠病进展中的作用仍有待阐明。
Intestinal parasite infections induce thymus-dependerit villus atrophy, but the effector mechanisms directly responsible for the development of villus atrophy are not thoroughly understood. In this Study, we analyzed the expression of cytotoxic factors or ligands in athymic nude rnu/rnu rats and their littermate euthyinic rnu/+ rats infected with the nematode Nippostrongylus brasiliensis. Morphometric analyses showed that partial villus atrophy developed 10 days after infection in euthymic but not in athymic rats, whereas crypt hyperplasia occurred in both types of: animal. Reverse transcription-polymerase chain reaction analyses of the isolated jejunal epithelial fraction showed that the development of villus atrophy in euthymic rats was positively correlated with an increase of granzyme B transcript levels but not with Fas ligand or tumor necrosis factor-alpha expression. In addition, the number of granzyme B-immunoreactive cells was increased significantly in euthymic rat villus epithelium and the propria mucosa after infection. The CD8(+) cell number did not change significantly. Collectively, these findings showed that significant increases in the number of cells that express the cytotoxic factor granzyme B occur in the nematode-infected small intestine of immunocompetent hosts. The type of cells that express granzyme B and their role in the progression of enteropathy remain to be elucidated.