The requirement for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in leukocyte-mediated immune glomerular injury
The requirement for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in leukocyte-mediated immune glomerular injury
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DOI：
10.1681/asn.v132350
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发表时间：
2002-02-01
影响因子：
13.6
通讯作者：
Holdsworth, SR
中科院分区：
文献类型：
--
作者：
Kitching, AR;Huang, XR;Holdsworth, SR
人类的炎症性肾小球肾炎的特征是肾小球中存在白细胞。粒细胞-巨噬细胞集落刺激因子（GM-CSF）和粒细胞集落刺激因子（G-CSF）可潜在地刺激或影响T细胞、巨噬细胞和中性粒细胞功能。为了确定GM-CSF和G-CSF在白细胞介导的肾小球肾炎中的作用，在遗传上缺乏GM-CSF（GM-CSF -/-小鼠）或G-CSF（G-CSF -/-小鼠）的小鼠中研究了肾小球损伤。研究了两种肾小球肾炎模型：嗜中性粒细胞介导的异相抗肾小球基底膜（GBM）肾小球肾炎和T细胞/巨噬细胞介导的新月体自体相抗GBM肾小球肾炎。与遗传正常（CSF WT）小鼠相比，GMCSF -/-和G-CSF -/-小鼠均免受异源期抗GBM肾小球肾炎的影响，蛋白尿和肾小球中性粒细胞数量减少。然而，只有GM-CSF小鼠在自体阶段免受新月体肾小球损伤，而G-CSF -/-小鼠没有受到保护，实际上肾小球中T细胞数量增加。对致肾炎抗原的体液反应不受GM-CSF或G-CSF缺乏的影响，但肾小球T细胞和巨噬细胞数量以及对致肾炎抗原的皮肤迟发型超敏反应在GM-CSF -/-小鼠中减少。这些研究表明，内源性GM-CSF在实验性肾小球肾炎中的自体和异源损伤阶段都起作用。
Proliferative glomerulonephritis in humans is characterized by the presence of leukocytes in glomeruli. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) can potentially stimulate or affect T cell, macrophage, and neutrophil function. To define the roles of GM-CSF and G-CSF in leukocyte-mediated glomerulonephritis, glomerular injury was studied in mice genetically deficient in either GM-CSF (GM-CSF -/- mice) or G-CSF (G-CSF -/- mice). Two models of glomerulonephritis were studied: neutrophil-mediated heterologous-phase anti-glomerular basement membrane (GBM) glomerulonephritis and T cell/macrophage-mediated crescentic autologous-phase anti-GBM glomerulonephritis. Both GMCSF -/- and G-CSF -/- mice were protected from heterologous-phase anti-GBM glomerulonephritis compared with genetically normal (CSF WT) mice, with reduced proteinuria and glomerular neutrophil numbers. However, only GM-CSF mice were protected from crescentic glomerular injury in the autologous phase, whereas G-CSF -/- mice were not protected and in fact had increased numbers of T cells in glomeruli. Humoral responses to the nephritogenic antigen were unaltered by deficiency of either GM-CSF or G-CSF, but glomerular T cell and macrophage numbers, as well as dermal delayed-type hypersensitivity to the nephritogenic antigen, were reduced in GM-CSF -/- mice. These studies demonstrate that endogenous GM-CSF plays a role in experimental glomerulonephritis in both the autologous and heterologous phases of injury.