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Relation of Helicobacter heilmannii infection to gastric MALT lymphoma formation in human and mouse

海尔曼螺杆菌感染与人和小鼠胃MALT淋巴瘤形成的关系

基本信息

批准号：
18590698
负责人：
NAKAMURA Masahiko
金额：
$ 2.32万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590698/
关键词：
Gastric MALT Lymohoma Helicobacter heilmannii VEGF Flt-1 Flk-1 Helicobacter pylori Helicobacter suis MALTリンパ腫 RCR法 in situ hybridization法 C57BL 6マウス apoptosis B cell lymphoma

项目摘要

1. Mouse Modelthe MALT lymphoma tissue was shown to have rich microvascular network consisting of the immature capillaries and venules, revealed by electron microscopy. By the immunohistochemical analysis, very much enhanced VEGF-A immunoreactivity was observed in the whole MALT lymphoma tissue, while VEGF-C immunoreactivity was observed only in the marginal area of the lymphoma. Both Flt-1 and Flk-1 were expressed in the lymphoma tissues. Flk-1 were mainly expressed in the immature endothelial cells, while Flt-1 were observed in the accumulated lymphocytes. The treatment with VEGF receptor monoclonal antibody significantly decreased the size of the protrusive lesion. In conclusion, VEGF-mediated mechanism was shown to play an important role in the expansion of the MALT lymphoma tissue induced by Hh infection in C57BL/6 mice.2. Human Casesout of 12 MALT lymphoma cases 4 cases were positive to Hp, 5 positive to HHLO and among them 4 cases were doubly positive to HHLO and Hp. By Fisher's exact test, HHLO infection as well as Hp and HHLO co-nfection was significantly related to the MALT lymphoma. By the analysis of urease gene, 4 cases were found to belong to Hs 'infection among 9 HHLO positive patients, while other cases were not identified to either Hh, Hs or Hf. By the in situ hybridization method, the Hh was recognized near the surface epithelial cells and fundic glandular cells including parietal cells, which coincided well with our previous infection study using C57BL/6 mice. On the other hand, 129 cases were positive to Hp and only 4 cases were positive to HHLO out of 221 non-MALT lymphoma cases. In conclusion, HHLO and Hp coinfection has shown to be closely related to MALT lymphoma in Japanese cases.

1.小鼠模型MALT淋巴瘤组织电镜下可见丰富的微血管网，由未成熟的毛细血管和微静脉组成。免疫组化结果显示，VEGF-A免疫反应在整个MALT淋巴瘤组织中均明显增强，而VEGF-C免疫反应仅在淋巴瘤的边缘区表达。Flt-1和Flk-1在淋巴瘤组织中均有表达。Flk-1主要表达于未成熟的内皮细胞，而Flt-1主要表达于聚集的淋巴细胞。VEGF受体单克隆抗体治疗可明显缩小肿胀病灶的大小。综上所述，VEGF介导的机制在Hh感染诱导的C57 BL/6小鼠MALT淋巴瘤组织扩张中起重要作用. 12例人类MALT淋巴瘤病例中，4例Hp阳性，5例HHLO阳性，其中4例HHLO和Hp双阳性。经Fisher精确检验，HHLO感染及Hp和HHLO共感染与MALT淋巴瘤的发生有显著相关性。9例HHLO阳性患者中，经尿素酶基因分析，4例为Hs '感染，其余均未鉴定为Hh、Hs或Hf。原位杂交结果显示，Hh主要分布在上皮细胞和胃底腺细胞（包括壁细胞）附近，这与我们以前用C57 BL/6小鼠进行的感染研究结果一致。221例非MALT淋巴瘤中Hp阳性129例，HHLO阳性4例。总之，HHLO和Hp的共同感染已被证明是密切相关的MALT淋巴瘤在日本的情况下。