A lymphocyte serine protease granzyme A causes detachment of a small-intestinal epithelial cell line (IEC-6)
A lymphocyte serine protease granzyme A causes detachment of a small-intestinal epithelial cell line (IEC-6)
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DOI：
10.1271/bbb.80140
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发表时间：
2008-09-01
影响因子：
1.6
通讯作者：
Fushiki, Tohru
中科院分区：
文献类型：
--
作者：
Hirayasu, Hirofumi;Yoshikawa, Yumiko;Fushiki, Tohru
粒酶 A (GzmA) 是一种在细胞毒性淋巴细胞中产生的丝氨酸蛋白酶（胰蛋白酶样特异性）。这种酶被认为可以进入病毒感染的细胞和正在生长的肿瘤并诱导细胞凋亡，但在散布于正常小肠上皮层的淋巴细胞中表达的 GzmA 的作用尚不清楚。在本研究中，发现重组大鼠 GzmA (rGzmA) 会引起非转化大鼠小肠上皮细胞系 IEC-6 的形态变化和脱离，尽管 rGzmA 处理的细胞作为聚集体脱离，没有细胞凋亡特征的变化。 rGzmA 诱导的变形和脱离发生在涂有 IV 型胶原和纤连蛋白的 IEC-6 细胞中，但不会发生在涂有层粘连蛋白的 IEC-6 细胞中。这些发现表明，正常小肠中的 GzmA 通过其裂解细胞外基质成分的能力，参与上皮细胞和基底膜之间粘附力的减少。
Granzyme A (GzmA) is a serine protease (trypsin-like specificity) produced in cytotoxic lymphocytes. This enzyme is believed to enter virus-infected cells and growing tumors and induce apoptosis, but the roles of GzmA expressed in lymphocytes scattered through the epithelial layer of the normal small intestine are unknown. In the present study, recombinant rat GzmA (rGzmA) was found to cause morphological changes and detachment of a non-transformed rat small-intestinal epithelial cell line IEC-6, although the rGzmA-treated cells detached as aggregates with no changes characteristic of apoptosis. rGzmA-induced deformation and detachment occurred in IEC-6 cells plated with collagen type IV and fibronectin, but not in those plated with laminin. These findings suggest that GzmA in the normal small intestine participates in the reduction of adhesion between epithelial cells and basement membranes, through its ability to cleave extracellular matrix components.