Weyts F A, Verburg-van Kemenade B M, Flik G, Lambert J G, Wendelaar Bonga S E
Department of Experimental Animal Morphology and Cell Biology, Agricultural University, Wageningen, 6700 AH, The Netherlands.
Brain Behav Immun. 1997 Jun;11(2):95-105. doi: 10.1006/brbi.1997.0484.
This is the first study to show that apoptosis as an immune regulatory mechanism is conserved in fish, demonstrating its importance in maintaining immunological homeostasis. The data further show that this mechanism is subject to control by glucocorticosteroids. Carp plasma cortisol concentrations increase from 20 to 434 ng/ml and cortisone from 5 to 50 ng/ml within 9 min of the onset of handling stress. At basal steroid concentrations in vitro, cortisol, but not its conversion product cortisone, inhibits proliferation of peripheral blood lymphocytes (PBL), as measured by [3H]thymidine incorporation. Induction of apoptosis in activated PBL is the apparent mechanism of cortisol action. In nonstimulated PBL cultures, apoptosis is induced by neglect (a lack of stimulating signals). Stimulation with LPS or PHA rescues lymphocytes from this type of apoptosis. Stimulated PBL populations, however, are sensitive to cortisol-induced apoptosis. Culture supernatants from activated PBL protect PBL from apoptosis by neglect, probably by supplying a growth signal. These supernatants, however, have no effect on cortisol-induced apoptosis.
这是第一项表明细胞凋亡作为一种免疫调节机制在鱼类中保守存在的研究，证明了其在维持免疫稳态中的重要性。数据进一步表明，该机制受糖皮质激素控制。在处理应激开始后的9分钟内，鲤鱼血浆皮质醇浓度从20纳克/毫升增加到434纳克/毫升，可的松从5纳克/毫升增加到50纳克/毫升。在体外基础类固醇浓度下，皮质醇而非其转化产物可的松抑制外周血淋巴细胞（PBL）的增殖，通过[3H]胸苷掺入法测量。皮质醇作用的明显机制是诱导活化的PBL发生凋亡。在未刺激的PBL培养物中，忽视（缺乏刺激信号）会诱导凋亡。用LPS或PHA刺激可使淋巴细胞免于这种类型的凋亡。然而，受刺激的PBL群体对皮质醇诱导的凋亡敏感。活化的PBL的培养上清液可能通过提供生长信号来保护PBL免于因忽视而导致的凋亡。然而，这些上清液对皮质醇诱导的凋亡没有影响。
