Masera R G, Gatti G, Bateman A, Solomon S, Sartori M L, Staurenghi A, Lazzero A, Griot G, Angeli A
Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino.
Ann Ital Med Int. 1993 Apr-Jun;8(2):80-5.
Corticostatins (CS)-defensins are a family of peptides recently isolated from neutrophils and cells of myeloid lineage. They have been termed CS in that members of the family inhibit ACTH-induced steroidogenesis, and defensins in that they are highly effective as enhancers of intracellular killing of pathogens. Natural killer (NK) cells are an immunocyte subset whose cytotoxic activity is modulated by lymphokines and hormones. Recent evidence suggests a myeloid origin for these cells. We evaluated whether two human CS-defensins, HP-1 and HP-4, are able to modulate in vitro spontaneous NK cell activity of human peripheral blood mononuclear (PBM) cells and in vitro susceptibility to the stimulatory effect by immune interferon (IFN-gamma) or interleukin 2 (IL-2) and to the inhibitory effect of cortisol. PBM cells were incubated for 20 h with HP-1 or HP-4 and IFN-gamma or IL-2 or cortisol. NK cell activity was measured in a 4-h direct cytotoxicity assay (K562 cells as a target). We also searched for CS-defensins in NK-enriched cell preparations by means of HPLC separation of the supernatant obtained from sonicated cells. HP-1 and HP-4 significantly inhibited both spontaneous and lymphokine-inducible NK cell activity, and potentiated cortisol-dependent inhibition. Radioimmunoassay on HPLC purified fractions demonstrated the presence of HP-1 in NK-enriched cell preparations. Our data indicate that HP-1 and HP-4 are negative modulators of NK cell cytotoxicity and that autocrine/paracrine mechanisms are conceivably involved. HP-1 production by NK cells may be viewed as additional support for the thesis of the myeloid origin of these immune effectors.
皮质抑素（CS）-防御素是最近从嗜中性粒细胞和髓系细胞中分离出的一类肽。它们被称为CS是因为该家族成员抑制促肾上腺皮质激素诱导的类固醇生成，被称为防御素是因为它们作为细胞内杀灭病原体的增强剂非常有效。自然杀伤（NK）细胞是一种免疫细胞亚群，其细胞毒性活性受淋巴因子和激素调节。最近的证据表明这些细胞起源于髓系。我们评估了两种人CS-防御素HP-1和HP-4是否能够在体外调节人外周血单个核（PBM）细胞的自发NK细胞活性，以及体外对免疫干扰素（IFN-γ）或白细胞介素2（IL-2）刺激作用和皮质醇抑制作用的敏感性。将PBM细胞与HP-1或HP-4以及IFN-γ或IL-2或皮质醇一起孵育20小时。在4小时的直接细胞毒性试验（以K562细胞为靶细胞）中测量NK细胞活性。我们还通过对超声处理细胞获得的上清液进行高效液相色谱分离，在富含NK细胞的制剂中寻找CS-防御素。HP-1和HP-4显著抑制自发的和淋巴因子诱导的NK细胞活性，并增强皮质醇依赖性抑制。对高效液相色谱纯化级分的放射免疫分析表明，在富含NK细胞的制剂中存在HP-1。我们的数据表明，HP-1和HP-4是NK细胞细胞毒性的负调节剂，并且可以想象自分泌/旁分泌机制参与其中。NK细胞产生HP-1可被视为对这些免疫效应器髓系起源论点的额外支持。
