Immunopathologic Study on The Mechanisms of Immune Complex Type Glomerulonephritis
Immunopathologic Study on The Mechanisms of Immune Complex Type Glomerulonephritis
批准号:
63480189
负责人:
MATSUO Seiichi
金额:
$3.58万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for General Scientific Research (B)
财政年份:
1988
资助国家:
日本
项目状态:
已结题
起止时间:
1988 至 1989
中文摘要
(1)大鼠实验性肾小球肾炎新模型的建立采用肾灌注技术,利用凝集素及其抗体建立以肾小球内皮表面抗体-抗原反应起始为特征的实验性肾小球肾炎模型。通过免疫组织学方法精确地研究了该实验模型的性质。(2)抗体与植入的凝集素相互作用后,肾小球内皮表面颗粒状免疫沉积的快速重新定位和形成被认为与细胞骨架的功能有关,因为在4ºC的实验中,使用Fab部分抗体代替完整的IgG分子,抑制了颗粒状免疫沉积的形成。或者用氯丙嗪。(3)初始免疫沉积后的动力学免疫沉积最初多形成于肾小球内皮表面,其定位迅速地向内皮下区转移,再向上皮下区转移。这一事实可以通过内皮细胞表面的免疫沉积,然后通过肾小球毛细血管壁的滤过压力来解释。这些观察结果与人类膜性肾小球肾病的发病机制有关。(4)培养肾小球细胞表面免疫沉积形成机制的研究利用培养的大鼠肾小球上皮细胞,植入细胞表面含有抗体和外源抗原的免疫复合物向细胞外结构脱落。(5)制备与肾小球及其致肾性反应的单克隆和多克隆抗体。获得兔抗唾液糖蛋白抗体,经hpa亲和柱层析纯化,命名为RBAHPA-PM。RBAHPA-PM与足细胞自由表面特异性反应,识别涉及n -聚糖的表位。RBAHPA-PM识别的抗原也存在于人肾小球中,这表明该抗原表位与某些人肾小球肾炎(如急性链球菌后肾小球肾炎)有关。几种单克隆抗体在大鼠体内的实验表明,这些抗体可诱导肾小球损伤。少
英文摘要
(1) Establishment of a new model of experimental glomerulonephritis in ratsA model of experimental glomerulonephritis characterized by the initiation of antibody-antigen reaction on the surface of glomerular endothelium was established by kidney perfusion technique using lectin(s) and its antibodies. The nature of this experimental model was studied precisely by immunohistologic methods.(2) Mechanisms of the formation of granular immune deposits on the surface of glomerular endothelium immediately after the interaction of antibodies and implanted lectinRapid relocalization and formation of granular immune deposits on the surface of glomerular endothelium was thought to be connected to the function of cytoskeleton because granular immune deposit formation was inhibited when experiments were carried out at 4゚C, using Fab fraction of antibodies instead of intact IgG molecules, or by the use of chlorpromazine.(3) Kinetics of immune deposits after the initial eventImmune deposits initially … More formed on the surface of glomerular endothelium changed their localization rather rapidly to the subendothelial area, and then to subepithelial area. This fact was explained by the shodding of immune deposits from the surface of endothelium and then by the filtration pressure across the glomerular capillary walls. These observations have relevance to the pathogenesis of human membranous glomerulonephropatliy.(4) Studies on the mechanisms of the formation of immune deposits on the surface of glomerular cells in cultureUsing rat glomerular epithelial cells in culture, immune complexes containing antibodies and foreign antigen planted on the cell surface were shed to the extracellular structure.(5) Production of monoclonal and polyclonal antibodies reacting with glomerulus and their nephritogenicityRabbit antibodies against sialoglycoprotein purified by the HPA-affinity column chromatography were obtained and named RBAHPA-PM. RBAHPA-PM reacted specifically with podocyte free surface and recognized the epitope(s) involving N-glycan. The antigen recognized by RBAHPA-PM was also present in human glomeruli suggesting that this epitope has relevance to certain human glomerulonephritides such as acute poststreptococcus glomerulonephritis. Several monoclonal antibodies were tested in rats and it was demonstrated that these antibodies could induce glomerular injury. Less
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吉田太: "glomerular injury induced by antibodies against heparan sulfate proteoglycan(HSPG) derived from PYS2 cells" Japanese Journal of Nephrology. 31. 15-23 (1989)
Futoshi Yoshida:“来自 PYS2 细胞的抗硫酸乙酰肝素蛋白多糖 (HSPG) 的抗体诱导的肾小球损伤”,日本肾脏病学杂志 31. 15-23 (1989)。
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平松武幸: Japanese Journal of Nephrology.(1989)
Takeyuki Hiramatsu:日本肾脏病学杂志。(1989)
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深津敦司: "The glomerular distribution of type IV collagen and laminin in human membranous glomerulonephritis." Human Pathology. 19. 64-68 (1988)
Atsushi Fukatsu:“人类膜性肾小球肾炎中 IV 型胶原和层粘连蛋白的肾小球分布。”19. 64-68 (1988)。
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吉田太: "Glomerular Injury induced by antifodies against heparan sulfate proteoglycan(HSPG)derived from PYS2 cells." Japanese Journal of Nephrology. 31. 15-23 (1989)
Futoshi Yoshida:“源自 PYS2 细胞的硫酸乙酰肝素蛋白聚糖 (HSPG) 抗体诱导的肾小球损伤。”日本肾脏病学杂志 31. 15-23 (1989)。
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HIRAMATSU T, MATSUO S, OKURA T, YOSHIDA F, WATANABE Y, SAKAMOTO N: "HEPARAN SULFATE PROTEOGLYCAN OF MURINE GLOMERULAR BASEMENT MEMBRANE: RELATIONSHIP BETWEEN LOCALIZATION OF THE CORE PROTEIN AND LOCALIZATION OF FIXED NEGATIVE CHARGES" Jpn J NEPHROL 31:5-1
HIRAMATSU T、松尾 S、OKURA T、吉田 F、渡边 Y、坂本 N:“鼠肾小球基底膜的硫酸乙酰肝素蛋白聚糖:核心蛋白定位与固定负电荷定位之间的关系”Jpn J NEPHROL 31:5-1
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海外基金