Crescentic glomerulonephritis is diminished in fibrinogen-deficient mice
Crescentic glomerulonephritis is diminished in fibrinogen-deficient mice
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DOI：
10.1152/ajprenal.0002.2001
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发表时间：
2001-12-01
影响因子：
4.2
通讯作者：
Tipping, PG
中科院分区：
文献类型：
--
作者：
Drew, AF;Tucker, HL;Tipping, PG
新月体形式的肾小球肾炎的特征在于纤维蛋白和细胞在鲍曼氏间隙中的积聚，并且与肾功能的快速丧失相关。纤维蛋白在肾小球簇中的积累被认为促进巨噬细胞浸润和肾小球损伤。为了直接探讨纤维蛋白（原）在新月体肾小球肾炎的发展中的作用，在纤维蛋白原缺陷和对照小鼠中诱导抗肾小球基底膜肾炎。对照小鼠的肾小球发生严重疾病，包括纤维蛋白沉积、炎性细胞积聚和新月体形成（肾小球的46.3 +/- 7.3%）。纤维蛋白原缺陷小鼠的疾病明显较轻，肾小球新月体较少（肾小球的24.0 ± 4.7%; P < 0.03）。相对于对照组小鼠（3.9 +/-1.4巨噬细胞/肾小球横截面; P < 0.03），纤维蛋白原缺陷小鼠（0.9 +/-0.4巨噬细胞/肾小球横截面）的肾小球巨噬细胞积聚减少。最后，通过血清肌酐评估的肾功能在纤维蛋白原缺陷小鼠中得到更好的维持。这些结果表明，虽然纤维蛋白（原）是不是必需的肾小球新月体的发展，它有助于显着的新月体肾小球肾炎的发病机制，通过促进肾小球巨噬细胞的积累和损害过滤。
Crescentic forms of glomerulonephritis are characterized by the accumulation of fibrin and cells in Bowman's space and are associated with a rapid loss of renal function. Accumulation of fibrin in the glomerular tufts is thought to promote macrophage infiltration and glomerular injury. To directly explore the role of fibrin(ogen) in the development of crescentic glomerulonephritis, antiglomerular basement membrane nephritis was induced in fibrinogen-deficient and control mice. Glomeruli from control mice developed severe disease including fibrin deposits, inflammatory cell accumulation, and crescent formation (46.3 +/- 7.3% of glomeruli). Fibrinogen-deficient mice developed significantly milder disease with fewer glomerular crescents (24.0 +/- 4.7% of glomeruli; P < 0.03). Glomerular macrophage accumulation was diminished in fibrinogen-deficient mice (0.9 +/- 0.4 macrophages/glomerular cross section) relative to control mice (3.9 +/- 1.4 macrophages/glomerular cross section; P < 0.03). Finally, renal function as assessed by serum creatinine was better maintained in fibrinogen-deficient mice. These results indicate that although fibrin( ogen) is not essential for the development of glomerular crescents, it contributes significantly to the pathogenesis of crescentic glomerulonephritis by promoting glomerular macrophage accumulation and impairing filtration.