Increased apoptosis and angiogenesis in gastric low-grade mucosa-associated lymphoid tissue-type lymphoma by Helicobacter heilmannii infection in C57/BL6 mice

Increased apoptosis and angiogenesis in gastric low-grade mucosa-associated lymphoid tissue-type lymphoma by Helicobacter heilmannii infection in C57/BL6 mice
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DOI:
10.1111/j.1574-695x.2007.00252.x
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发表时间:
2007-07-01
影响因子:
--
通讯作者:
Tsuchimoto, Kanji
Tsuchimoto, Kanji
中科院分区:
其他
文献类型:
--
作者:
Nishikawa, Kaori;Nakamura, Masahiko;Tsuchimoto, Kanji

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海尔曼氏幽门螺杆菌可引起胃低度恶性黏膜相关淋巴组织型(MALT)淋巴瘤,但其确切的病理生理机制尚不清楚。我们最近通过经口感染主要来源于食蟹猴的H.heilmannii建立了C57BL/6小鼠胃B细胞MALT淋巴瘤模型。利用该模型,对MALT淋巴瘤进行了肉眼、免疫组织化学和电子显微镜观察,以观察细胞凋亡和血管生成的发展。感染组小鼠胃MALT淋巴瘤组织中心区微血管网明显增强,血管内皮生长因子-A表达增强,边缘可见血管内皮生长因子-C表达。此外,许多被海尔曼氏杆菌侵袭的壁细胞在MALT淋巴瘤周围的胃底粘膜组织中显示caspase-3免疫反应。综上所述,在H.heilmannii诱导的MALT淋巴瘤中,血管内皮生长因子-A和因子-C的免疫反应在壁细胞凋亡增加的周围区域被观察到增强,这表明血管生成和细胞凋亡在MALT淋巴瘤的形成中具有病理生理学意义。
Helicobacter heilmannii has been reported to cause gastric low-grade mucosa-associated lymphoid tissue-type (MALT) lymphoma, but its precise pathophysiological mechanism remains to be clarified. We recently established a model of gastric B-cell MALT lymphoma in C57BL/6 mice by means of peroral infection of H. heilmannii primarily obtained from cynomolgus monkeys. Using this model, macroscopic, immunohistochemical, and electron microscopic observations of MALT lymphomas were carried out in order to examine the development of apoptosis and angiogenesis. Enhancement of the microvascular network and an increase in vascular endothelial growth factor-A were detected in the central region of the MALT lymphoma tissue in the infected mouse stomach, while vascular endothelial growth factor-C was detected at the margins of the MALT lymphomas. In addition, many H. heilmannii-invaded parietal cells showed caspase-3 immunoreactivity in the fundic mucosal tissue surrounding the MALT lymphoma. In conclusion, in H. heilmannii-induced MALT lymphoma, enhanced immunoreactivity of vascular endothelial growth factor-A and factor-C was observed in areas encircled by increased parietal cell apoptosis, which indicates the pathophysiological relevance of both angiogenesis and apoptosis in MALT lymphoma formation.