Lefkowith J B, Schreiner G
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
J Clin Invest. 1987 Oct;80(4):947-56. doi: 10.1172/JCI113187.
Essential fatty acid (EFA) deficiency exerts a beneficial effect on immune-mediated glomerulonephritis, preventing both the tissue injury and consequent mortality. Because both macrophages and eicosanoids are thought to play pathogenic roles in glomerulonephritis, and because macrophages play an important role in modulating arachidonate metabolism at sites of renal injury, the effects of EFA deficiency on the population of resident glomerular macrophages and on glomerular eicosanoid generation were examined. EFA deficiency led to a striking reduction in the number of resident glomerular macrophages and a corresponding reduction in the number of resident glomerular Ia+ cells. This phenomenon was not strain-specific, was not due to a decrease in circulating monocytes, was not a function of changes in cell surface labeling characteristics, and was not restricted to a specific subset of glomeruli. In addition, EFA deficiency affected other areas of the renal cortex: a comparable depletion of interstitial macrophages and Ia+ cells was also observed. In conjunction with the decrease in glomerular macrophages seen with the deficiency state, a marked decrease in both basal and angiotensin II-stimulated glomerular eicosanoid production was noted. In contrast to angiotensin II, platelet-activating factor-induced eicosanoid production was not significantly affected by the deficiency state. These changes in glomerular eicosanoid production could not be attributed to changes in glomerular cyclooxygenase or reacylation capacity. Dietary (n-6) fatty acid supplementation, but not (n-3) fatty acid supplementation, reversed both the decrease in glomerular macrophages and the diminished eicosanoid metabolism seen with the deficiency state. Understanding the mechanisms behind the changes in the glomerular microenvironment induced by EFA deficiency may provide a basis for elucidating the protective effect of dietary fatty acid manipulation on immune-mediated glomerulonephritis.
必需脂肪酸（EFA）缺乏对免疫介导的肾小球肾炎具有有益作用，可预防组织损伤及随之而来的死亡。由于巨噬细胞和类花生酸都被认为在肾小球肾炎中发挥致病作用，且巨噬细胞在肾损伤部位调节花生四烯酸代谢中起重要作用，因此研究了EFA缺乏对肾小球固有巨噬细胞数量及肾小球类花生酸生成的影响。EFA缺乏导致肾小球固有巨噬细胞数量显著减少，同时肾小球固有Ia +细胞数量相应减少。这种现象并非特定品系所特有，不是由于循环单核细胞减少所致，不是细胞表面标记特征变化的结果，也不限于特定的肾小球亚群。此外，EFA缺乏影响肾皮质的其他区域：还观察到间质巨噬细胞和Ia +细胞有类似的减少。与缺乏状态下肾小球巨噬细胞减少同时出现的是，基础及血管紧张素II刺激的肾小球类花生酸生成均显著减少。与血管紧张素II不同，血小板活化因子诱导的类花生酸生成不受缺乏状态的显著影响。肾小球类花生酸生成的这些变化不能归因于肾小球环氧化酶或再酰化能力的改变。膳食补充（n-6）脂肪酸而非（n-3）脂肪酸可逆转缺乏状态下出现的肾小球巨噬细胞减少及类花生酸代谢减弱的情况。了解EFA缺乏引起的肾小球微环境变化背后的机制，可能为阐明膳食脂肪酸调控对免疫介导的肾小球肾炎的保护作用提供基础。
