Failure to induce anti-glomerular basement membrane glomerulonephritis in TNFα/β deficient mice
Failure to induce anti-glomerular basement membrane glomerulonephritis in TNFα/β deficient mice
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DOI：
10.1046/j.1365-2613.1998.00080.x
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发表时间：
1998-12-01
影响因子：
3
通讯作者：
Le Hir, M
中科院分区：
文献类型：
--
作者：
Ryffel, B;Eugster, H;Le Hir, M
TNF是一种关键的促炎细胞因子，在炎症细胞募集所需的内皮粘附分子的表达中起核心作用。抗gem抗体诱导的增殖性肾小球肾炎的特点是炎症细胞聚集到肾小球和毛细血管损伤，然后再生成新月状。肾小球病理可能是由于TNF诱导，因此我们在TNF α / β缺陷小鼠中验证了这一假设。在致敏野生型小鼠中给予抗gem抗体导致免疫复合物和补体因子3的沉积，随后增加ICAM-1和VCAM-1的表达和多形核白细胞的内流。明显的蛋白尿先于增殖性肾小球肾炎，肾小球新月状形成，在10天完全发育。相比之下，TNF α / β缺乏小鼠没有发生肾小球肾炎。类似的抗体复合物沉积也被发现，但在TNF α / β缺乏的小鼠中，ICAM-1和VCAM-1的上调、炎症细胞的涌入和随后的组织损伤是不存在的。因此，我们得出结论，TNF通过阻止内皮粘附分子的上调和随后的增殖性肾小球肾炎的发展，在炎症细胞的募集中起关键作用。
TNF is a key proinflammatory cytokine playing a central role in the expression of endothelial adhesion molecules required for the recruitment of inflammatory cells. Proliferative glomerulonephritis induced by anti-GEM antibody is characterized by the recruitment of inflammatory cells into the glomerulus and capillary damage followed by regeneration with crescent formation. The glomerular pathology may be due to TNF induction and we therefore tested this hypothesis in TNF alpha/beta deficient mice. Anti-GEM antibody administration in sensitised wild-type mice resulted in deposition of immune complexes and complement factor 3, followed by increased ICAM-1 and VCAM-1 expression and influx of polymorphonucelar leucocytes. Distinct proteinuria precedes proliferative glomerulonephritis with glomerular crescent formation, which is fully developed at 10 days. By contrast, no glomerulonephritis developed in TNF alpha/beta deficient mice. Comparable antibody complex deposits are found, but the upregulation of ICAM-1 and VCAM-1, the influx of inflammatory cells and the subsequent tissue damage is absent in TNF alpha/beta deficient mice. Therefore, we conclude that TNF plays a key role for the recruitment of inflammatory cells by preventing the upregulation of endothelial adhesion molecule and the subsequent development of proliferative glomerulonephritis.