Jansen A, Lewis S, Cattell V, Cook H T
Department of Histopathology, St. Mary's Medical School, Imperial College of Science, Technology and Medicine, London, England, United Kingdom.
Kidney Int. 1992 Nov;42(5):1107-12. doi: 10.1038/ki.1992.394.
L-arginine can be metabolized to nitric oxide (NO) by nitric oxide synthase (NOS) and to urea and L-ornithine by arginase. Competition between these pathways for L-arginine in inflammatory sites has been suggested. In experimental glomerulonephritis glomeruli produce nitrite; a major source is macrophages. We hypothesized that arginase is present in glomeruli and may compete for substrate with NOS in glomerulonephritis. Therefore we examined both pathways in isolated nephritic glomeruli and peritoneal macrophages. Arginase activity was present in glomeruli, increased by > 500% in nephritic glomeruli compared to controls, and was predominant over NOS. Activity increased with L-NMMA (a NOS inhibitor), but this trend did not reach statistical significance. In macrophages both pathways were present; NOS predominated basally but this was reversed by L-NMMA. In contrast with glomeruli macrophage arginase activity increased after LPS stimulation. Levels of macrophage arginase activity could not account for activity in nephritic glomeruli, suggesting another source of arginase. This is the first demonstration of high arginase activity of nephritic glomeruli. Competition between arginase and NOS pathways suggests a regulatory mechanism of L-arginine metabolism within the glomerulus, with implications for the pathogenesis of injury and scarring in glomerulonephritis.
L-精氨酸可通过一氧化氮合酶（NOS）代谢为一氧化氮（NO），并通过精氨酸酶代谢为尿素和L-鸟氨酸。有人提出，在炎症部位，这些途径会竞争L-精氨酸。在实验性肾小球肾炎中，肾小球会产生亚硝酸盐，其主要来源是巨噬细胞。我们假设精氨酸酶存在于肾小球中，并且在肾小球肾炎中可能会与NOS竞争底物。因此，我们在分离的肾炎性肾小球和腹膜巨噬细胞中研究了这两种途径。精氨酸酶活性存在于肾小球中，与对照组相比，肾炎性肾小球中的活性增加了500%以上，且占主导地位超过NOS。活性随L-NMMA（一种NOS抑制剂）增加，但这种趋势未达到统计学意义。在巨噬细胞中，两种途径均存在；基础状态下NOS占主导，但L-NMMA可使其逆转。与肾小球相反，巨噬细胞精氨酸酶活性在LPS刺激后增加。巨噬细胞精氨酸酶活性水平无法解释肾炎性肾小球中的活性，提示存在精氨酸酶的另一个来源。这是首次证明肾炎性肾小球具有高精氨酸酶活性。精氨酸酶和NOS途径之间的竞争提示了肾小球内L-精氨酸代谢的一种调节机制，对肾小球肾炎中损伤和瘢痕形成的发病机制具有重要意义。
