Masera R G, Bateman A, Muscettola M, Solomon S, Angeli A
Dipartimento di Scienze Cliniche e Biologiche, Università di Torina, Italy.
Regul Pept. 1996 Apr 9;62(1):13-21. doi: 10.1016/0167-0115(95)00150-6.
Corticostatins/defensins are a family of cationic peptides recently isolated from phagocytotic cells of the myeloid lineage. Natural killer (NK) cells are spontaneously cytotoxic large granular lymphocytes that are involved in immunosurveillance against cancer and infections. Their activity is modulated by hormones of the hypothalamic-pituitary-adrenal axis. We wished to determine whether two human corticostatins/defensins, HP-1 and HP-4, are able to change in vitro the spontaneous NK activity of human peripheral blood mononuclear cells (PBMC) and the responses either to the stimulatory cytokines immune interferon (IFN-gamma) or interleukin 2 (IL-2) and to the inhibitory hormone cortisol. NK cell activity was measured in a 4-h direct cytotoxicity assay with K562 cells as a target. HP-1 and HP-4 (10 (-8) -10 (-9) M) significantly inhibited the spontaneous and cytokine-inducible NK activity, and increased the cortisol-dependent inhibition. Radioimmunoassay of HPLC purified fractions obtained from sonicated NK cells showed HP-1 in the two cell preparations examined. We also evaluated the effects of HP-1 and HP-4 (10 (-8) M -10(-9) M) upo IFN-gamma and interleukin 6 (IL-6) production by PBMC stimulated with phytohemagglutinin (PHA) or concanavalin A (ConA). IFN-gamma was titrated with the biological assay using WISH cells as indicators and vescicular stomatitis virus (VSV) as the challenge virus. IL-6 was measured using an enzyme amplified sensitivity immunoassay. Both HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that corticostatins/defensins are novel modulators of lymphocyte functions in vitro. Their immunodepressing properties could add complexity and plasticity to hypothalamic-pituitary-adrenal-cytokine circuits in vivo.
皮质抑素/防御素是最近从髓系吞噬细胞中分离出的一类阳离子肽。自然杀伤（NK）细胞是具有自发细胞毒性的大颗粒淋巴细胞，参与对癌症和感染的免疫监视。它们的活性受下丘脑 - 垂体 - 肾上腺轴激素的调节。我们希望确定两种人皮质抑素/防御素HP - 1和HP - 4是否能够在体外改变人外周血单个核细胞（PBMC）的自发NK活性以及对刺激性细胞因子免疫干扰素（IFN - γ）或白细胞介素2（IL - 2）和抑制性激素皮质醇的反应。在以K562细胞为靶标的4小时直接细胞毒性试验中测量NK细胞活性。HP - 1和HP - 4（10^(-8) - 10^(-9) M）显著抑制自发和细胞因子诱导的NK活性，并增强皮质醇依赖性抑制。对从超声处理的NK细胞获得的HPLC纯化级分进行放射免疫测定，在所检测的两种细胞制剂中均显示有HP - 1。我们还评估了HP - 1和HP - 4（10^(-8) M - 10^(-9) M）对用植物血凝素（PHA）或刀豆球蛋白A（ConA）刺激的PBMC产生IFN - γ和白细胞介素6（IL - 6）的影响。使用WISH细胞作为指标并以水泡性口炎病毒（VSV）作为攻击病毒，通过生物学测定法滴定IFN - γ。使用酶放大灵敏度免疫测定法测量IL - 6。HP - 1和HP - 4均显著降低细胞因子的产生。我们的数据表明，皮质抑素/防御素是体外淋巴细胞功能的新型调节剂。它们的免疫抑制特性可能会增加体内下丘脑 - 垂体 - 肾上腺 - 细胞因子回路的复杂性和可塑性。
