Regulation of macrophage functions by cytokine and 1,25-dihydroxyvtamin D_3 on glomerulonephritis

细胞因子和1,25-二羟基维生素D_3对肾小球肾炎巨噬细胞功能的调节

• 批准号: 06670217
• 负责人: ORIKASA Michiaki
• 金额: $ 1.41万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670217/
• 关键词: macrophage; podocyte; colony-stimulating factors; 1,25-dihydroxyvitamin D_3; crescent-forming cells; glomerulonephritis.; 糸球体培養; サイトカイン; M-CSF; IFN

One representative of a number of severe lesions that occur outside the glomerular capillaries and involve podocytes is crescentic glomerulonephritis. The question of whether the crescent-forming cells are derived from glomerular epithelial cells or monocytes/macrophages is highly controversial and has not yet been clarified. To investigate pathophysiology of podocyte in crescentic glomerulonephritis, we attempted to establish methods for culturing cells confirmed to be derived from podocytes, focusing particularly on the relationship between podocytes and macrophages.Non-adherent cells of unknown origin that grew from normal rat isolated glomerular cultures increased in number, reaching a total of 3.5 x 10^5/ml on day 11. They showed several characteristics of macrophages, the expression of specific antigens and enzyme, morphology, and production of H_2O_2. They expressed FxlA,but lacked the expressions of Thy1.1 or factor VIII.A morphological kinetic study on day 3-11 of culture show … More ed that the cells with foot processes on the glomerular basement membrane (GBM) changed into macrophagic cells (MC) and migrated from the glomeruli. Immunofluorescence double staining indicated that the cells migrated from glomerular surface on day 8 were both anti-podocalyxin and ED-1 positive. Furthermore, immunoelectron microscopy revealed that the ED-1 positive cells were located on GBM.Pretreatment with an anti-macrophages and -Thy1.1 antibodies both with complement did not reduce the number of MC,while pretreatment with puromycin aminonucleoside predominantly reduced the number of MC.Predominant decrease in the number of glomerular macrophage by gamma-irradiation did not result in the reduction in the number of MC.MC derived from glomerular cultures of bone marrow chimeric rats expressed the Ia antigen originated from recipient, indicating that MC is not derived from bone marrow cells. Macrophage colony-stimulating factor accelerated the speed of the change into MC and granulocyte-macrophage colony-stimulating factor dramatically enhanced its degree with increase of cell number on day 8.We concluded that podocytes change into MC in normal rat glomerular culture and the change is enhanced by CSFs. The results provide a completely new insight into the origin of crescent forming cells. Less

月牙状肾小球肾炎是发生在肾小球毛细血管外并累及足细胞的严重病变的一个代表。月牙形细胞是否来源于肾小球上皮细胞或单核/巨噬细胞的问题是高度争议的，尚未澄清。为了研究月牙状肾小球肾炎足细胞的病理生理，我们试图建立证实来源于足细胞的细胞培养方法，重点研究足细胞与巨噬细胞的关系。从正常大鼠离体肾小球培养物中生长的来源不明的非贴壁细胞数量增加，在第11天达到3.5 × 10^5/ml。它们表现出巨噬细胞的一些特征，特异性抗原和酶的表达，形态和H_2O_2的产生。他们表达FxlA，但缺乏Thy1.1或因子VIII的表达。培养第3 ~ 11天的形态学动力学研究表明，在肾小球基底膜（glomerular basal membrane， GBM）上有足突的细胞转变为巨噬细胞（macrophagic cells， MC）并从肾小球中迁移出来。免疫荧光双染色显示第8天从肾小球表面迁移的细胞抗足alyxin阳性，ED-1阳性。此外，免疫电镜显示ED-1阳性细胞位于GBM上。用抗巨噬细胞和-Thy1.1抗体（均为补体）预处理后，MC的数量没有减少，而用嘌呤霉素氨基核苷预处理后，MC的数量明显减少。γ -照射对肾小球巨噬细胞数量的显著减少没有导致MC的数量减少。表明MC不是来源于骨髓细胞。在第8天，巨噬细胞集落刺激因子加速了向MC转变的速度，粒细胞-巨噬细胞集落刺激因子的转变程度随着细胞数量的增加而显著增强。我们认为足细胞在正常大鼠肾小球培养中转变为MC， csf增强了这种转变。这些结果为新月形细胞的起源提供了全新的见解。少

项目成果

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Kawase T.et al.：“1,25-二羟基维生素D_3 促进前列腺素E_1 诱导HL-60 细胞分化。”

Fujigaki Y.et al.: "Structural continuity of filtration slit (slit diaphragm) to plasma membrane of podocyte." Kidney Int.50. 54-62 (1996)

Fujigaki Y.et al.：“过滤狭缝（狭缝隔膜）与足细胞质膜的结构连续性。”

Kawase T.et al.: "Protein tyrosine phosphorylation induced by epidermal growth tactor and insulin-like growth factor-I in a rat clonal dental pulp-cell line." Archiv.oral Biol.40. 921-929 (1995)

Kawase T.等人：“在大鼠克隆牙髓细胞系中，表皮生长因子和胰岛素样生长因子-I 诱导蛋白质酪氨酸磷酸化。”

Cheng Q.L.et al.: "Progressive renal lesions induced by administration of monoclonal antibody 1-22-3 to unilaterally nephrectomized rats." Clin.Exp.Immunol.102. 181-185 (1995)

Cheng Q.L.等人：“对单侧肾切除大鼠施用单克隆抗体 1-22-3 诱导进行性肾损伤。”

Orikasa M.et al.: "Macrophagic cells outgrowth from normal rat glomerular culture-Possible metaplastic change from podocytes-." Lab.Invest.75. 719-733 (1996)

Orikasa M.等人：“正常大鼠肾小球培养物中长出的巨噬细胞-可能是足细胞的化生变化-”。