Experimental analysis on organ allergy of hapten-bound renal tubular basement membrane

半抗原结合肾小管基底膜器官过敏的实验分析

• 批准号: 05670211
• 负责人: JOH Kensuke
• 金额: $ 1.34万
• 依托单位: The JIKEI University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670211/
• 关键词: Hapten; Trinitrophenol; Renal tubular basement membrane; Organ allergy; Cationic protein; Ovalbumin; Cellular immunity; Interstitial nephritis; trinitrophenol; 卵白アルブミン

Trinitrophenol-conjugated ovalbumin was highly cationized (isoelectric point>10) and was subjected to gel filtration to obtain monomer (42 kDa). The antigen was injected selectively into the left renal arteries of Wistar rats. Antigen localization was documented by immunohistochemistry on frozen section ; it was deposited in a liner pattern on the tubular basement membrane (TBM) and Bowman's capsule but not on the glomerular basement membrane, and remained up to 36 h after the antigen injection. In control, non-cationized, monomeric TNP-OA (42 kDa, isoelectric point=4.6) showed fine granular deposition in the tubular epithelium exclusivery, but not on the TBM.Tubulointerstitial nephritis (TIN) with neutrophilic infiltration was induced by the serum transfer of antiTNP-human IgG rabbit serum 24 h after cationic antigen injection. Acute tubular necrosis was induced after cationic antigen injection in the rats which were 7 days-previously skin-sensitized by picryl chloride to have TNP-specific cellular immunity. The lesion was not similar to the lesion of human hypersensitivity nephritis and may due to the TNP-toxicity. The transfer of splenic T cell (either CD4+ or CD8+) against TNP did not contribute to TIN-induction in the non-sensitized C57/BL6 mice which were previously injected with the cationic antigen.

将三硝基苯酚偶联的卵清蛋白高度阳离子化(等电点为10)，经凝胶过滤得到42 kDa的单体。将该抗原选择性注入Wistar大鼠左肾动脉。冰冻切片免疫组织化学染色证实，抗原定位于肾小管上皮细胞基底膜和包膜上，呈线状沉积在肾小球基底膜上，而在肾小球基底膜上未见分布，注射抗原后36h仍可见。对照组，非阳离子单体TNP-OA(42 kDa，等电点=4.6)在肾小管上皮细胞内可见细小颗粒状沉积，但在肾小管上皮细胞上无明显颗粒沉积。皮下注射阳离子抗原7天后致敏大鼠急性肾小管坏死，使大鼠产生TNP特异性细胞免疫。该病变与人过敏性肾炎的病变不同，可能与TNP毒性有关。在先前注射阳离子抗原的非致敏C57/BL6小鼠中，针对TNP的脾T细胞(CD4+或CD8+)的转移不有助于TIN的诱导。

项目成果

Joh K et al.: "Morphologic variations of dense deposit disease : Light and electron microscopic immunohistochemical and clinical findings in 10 patients." Acta Pathol Jpn. 43. 552-565 (1993)

Joh K 等人：“致密沉积病的形态变化：10 名患者的光镜和电子显微镜免疫组织化学和临床发现。”

Kensuke Joh: "Antigenicities of enteropathogenic Escherichia coli,lysozyme,and alpha-1-antichymotrypsin on macrophages of genitourinary malacoplakia" Pathology International. 45. 215-226 (1995)

Kensuke Joh：“肠病性大肠杆菌、溶菌酶和 α-1-抗胰凝乳蛋白酶对泌尿生殖系统软斑病巨噬细胞的抗原性”国际病理学。

Yasuhiro Suzuki: "MHC class 1 gene(s) in the D/L region but not the TNF-α gene determines development of toxoplasmic encephalitis in mice" The Journal of Immunology. 153. 4649-4654 (1994)

Yasuhiro Suzuki：“D/L 区域中的 MHC 1 类基因而非 TNF-α 基因决定小鼠弓形虫脑炎的发生”《免疫学杂志》153. 4649-4654 (1994)。

Kiyoshi Ohkawa: "Pyridoxal kinase immunoreactivity in rabbit brain" Neurochemical Research. 19. 1231-1235 (1994)

Kiyoshi Ohkawa：“兔脑中的吡哆醛激酶免疫反应性”神经化学研究。

Kiyoshi Ohkawa: "Bovine serum albumin-Doxorubicin conjugate overcomes multidrug resistance in a rat hepatoma" Cancer Reseach. 53. 4238-4242 (1993)

Kiyoshi Ohkawa：“牛血清白蛋白-阿霉素结合物克服了大鼠肝癌的多药耐药性”癌症研究。