Ignarro L J, Lint T F, George W J
J Exp Med. 1974 Jun 1;139(6):1395-414. doi: 10.1084/jem.139.6.1395.
The purpose of this investigation was to examine the effects of autonomic neurohormones, cyclic nucleotides, and related agents on the immunologic discharge of lysosomal enzymes from, and phagocytosis by, purified human neutrophils. In order to discern the possible intracellular mechanisms by which certain neurohormones influence neutrophil function, the concentrations of cyclic AMP and cyclic GMP in neutrophils were assessed during cell contact with phagocytizable particles and autonomic agents. The model system employed for study was the interaction of purified human neutrophils with rheumatoid arthritic (RA) serum-treated zymosan particles at 37 degrees C in a neutral, balanced salt solution containing glucose. Neutrophils ingested the particles and discharged beta-glucuronidase but not lactate dehydrogenase activity during 30 min of incubation. Treatment of zymosan particles with RA serum was more effective than treatment with normal serum with regard to the extent of both particle uptake and lysosomal enzyme release. During contact of neutrophils with RA serum-treated zymosan particles epinephrine, isoproterenol, and cyclic AMP inhibited both particle ingestion and beta-glucuronidase discharge. These actions of epinephrine were associated with a concomitant elevation of cyclic AMP levels. In contrast to the actions of catecholamines and cyclic AMP, acetylcholine and cyclic GMP accelerated lysosomal enzyme release without affecting particle uptake. The actions of acetylcholine were associated with a concomitant elevation of cyclic GMP levels. Increases in neutrophil levels of cyclic GMP but not of cyclic AMP were associated also with the discharge of beta-glucuronidase provoked by particles in the absence of added cholinergic agents. The data suggest that the immunologic release of lysosomal enzymes from human neutrophils can be regulated by autonomic neurohormones, perhaps via the selective formation of appropriate nucleotides.
本研究的目的是检测自主神经激素、环核苷酸及相关药物对纯化的人中性粒细胞溶酶体酶免疫释放及吞噬作用的影响。为了弄清某些神经激素影响中性粒细胞功能的可能细胞内机制，在细胞与可吞噬颗粒及自主神经药物接触期间，评估了中性粒细胞中环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）的浓度。用于研究的模型系统是纯化的人中性粒细胞与经类风湿性关节炎（RA）血清处理的酵母聚糖颗粒在37℃下于含葡萄糖的中性平衡盐溶液中的相互作用。中性粒细胞在孵育30分钟期间摄取颗粒并释放β-葡萄糖醛酸酶，但不释放乳酸脱氢酶活性。就颗粒摄取和溶酶体酶释放的程度而言，用RA血清处理酵母聚糖颗粒比用正常血清处理更有效。在中性粒细胞与经RA血清处理的酵母聚糖颗粒接触期间，肾上腺素、异丙肾上腺素和cAMP抑制颗粒摄取和β-葡萄糖醛酸酶释放。肾上腺素的这些作用与cAMP水平的同时升高有关。与儿茶酚胺和cAMP的作用相反，乙酰胆碱和cGMP加速溶酶体酶释放而不影响颗粒摄取。乙酰胆碱的作用与cGMP水平的同时升高有关。在没有添加胆碱能药物的情况下，中性粒细胞中cGMP水平升高而非cAMP水平升高也与颗粒引发的β-葡萄糖醛酸酶释放有关。数据表明，人中性粒细胞溶酶体酶的免疫释放可能受自主神经激素调节，或许是通过选择性形成合适的核苷酸来实现的。
