Carlstedt-Duke J, Brönnegård M, Strandvik B
Proc Natl Acad Sci U S A. 1986 Dec;83(23):9202-6. doi: 10.1073/pnas.83.23.9202.
The regulation of arachidonic acid release from membrane phospholipids was investigated in lymphocytes from patients with cystic fibrosis as well as control patients. No effect of either dexamethasone or fetal calf serum was seen on arachidonic acid release from cystic fibrosis lymphocytes, in contrast to control lymphocytes. In the latter cells, arachidonic acid release was inhibited by dexamethasone, fetal calf serum, or both. There were no differences in glucocorticoid receptor in lymphocytes from the two groups with regard to Kd and number of binding sites per cell. Furthermore, dexamethasone inhibited the incorporation of thymidine into lymphocytes from either group, indicating a normal functional glucocorticoid receptor. The defective regulation of arachidonic acid, resulting in an increased turnover, can explain many of the findings in cystic fibrosis, and we hypothesize that it is the basic defect causing the disease. The defect occurs at a level after the glucocorticoid receptor, which is functionally normal, and involves either the glucocorticoid-dependent phospholipase-inhibitory protein lipomodulin (lipocortin) or phospholipase A2.
对囊性纤维化患者以及对照患者的淋巴细胞中花生四烯酸从膜磷脂释放的调节进行了研究。与对照淋巴细胞相比，地塞米松或胎牛血清对囊性纤维化淋巴细胞中花生四烯酸的释放均无影响。在对照淋巴细胞中，花生四烯酸的释放受到地塞米松、胎牛血清或两者的抑制。两组淋巴细胞中的糖皮质激素受体在解离常数（Kd）和每个细胞的结合位点数量方面没有差异。此外，地塞米松抑制两组淋巴细胞中胸腺嘧啶核苷的掺入，表明糖皮质激素受体功能正常。花生四烯酸调节缺陷导致其周转增加，这可以解释囊性纤维化中的许多发现，我们推测这是导致该疾病的根本缺陷。该缺陷发生在功能正常的糖皮质激素受体之后的水平，涉及糖皮质激素依赖性磷脂酶抑制蛋白脂调素（脂皮质蛋白）或磷脂酶A2。
