Departamento de Imunobiologia, Instituto de Biologia, Universidade Federal Fluminense, Niterói, Brazil.
Programa de Pós Graduação em Patologia Universidade Federal Fluminense, Niterói, Brazil.
Neuroimmunomodulation. 2019;26(4):188-197. doi: 10.1159/000501720. Epub 2019 Aug 14.
Ouabain (OUA) is a cardiotonic glycoside originally extracted from African plants. It has also been described as an endogenous component in mammals, being released in stress situations mainly by the adrenal gland. OUA has been reported to be capable of inhibiting mitogen-induced lymphocyte proliferation and also affects B and T lymphocytes.
The aim of this work is to show the effects of OUA in peripheral T lymphocytes.
In the in vivo experiments, mice were injected intraperitoneally for 3 consecutive days with RPMI medium (control group) or 0.56 mg/kg of OUA diluted in RPMI medium (OUA group). On the fourth day, spleen or mesenteric lymph nodes were removed.
OUA significantly reduced the number of CD4+ T lymphocytes in the spleen, especially regulatory T cells (Tregs). In vitro OUA did not inhibit the proliferation of CD4+T lymphocytes stimulated with anti-CD3 neither was able to induce the apoptosis of CD4+ nor Tregs. There was no increase in the number or percentage of T lymphocytes in the mesenteric lymph nodes, suggesting that there was no preferential accumulation of these cells in this organ. Secretion of IL-2 by activated T lymphocytes was decreased by the OUA, explaining at least in part the reduction of Tregs, since this cytokine is involved in the peripheral conversion and maintenance of Tregs.
The impact of this reduction in autoimmune diseases, allergy and cancer as well as the potential use of OUA as a therapeutic approach in tumor treatment still needs more investigation.
哇巴因(OUA)最初是从非洲植物中提取的强心糖苷。它也被描述为哺乳动物中的内源性成分,主要由肾上腺在应激情况下释放。有报道称,OUA 能够抑制有丝分裂原诱导的淋巴细胞增殖,并且还影响 B 和 T 淋巴细胞。
本工作旨在展示 OUA 在周围 T 淋巴细胞中的作用。
在体内实验中,小鼠连续 3 天经腹腔注射 RPMI 培养基(对照组)或 RPMI 培养基中 0.56mg/kg 的 OUA(OUA 组)。第四天,取出脾脏或肠系膜淋巴结。
OUA 显著减少了脾脏中 CD4+T 淋巴细胞的数量,尤其是调节性 T 细胞(Tregs)。在体外,OUA 既不能抑制抗 CD3 刺激的 CD4+T 淋巴细胞的增殖,也不能诱导 CD4+或 Tregs 的凋亡。肠系膜淋巴结中 T 淋巴细胞的数量或百分比没有增加,这表明这些细胞没有优先积聚在这个器官中。激活的 T 淋巴细胞分泌的 IL-2 减少了 OUA,这至少部分解释了 Tregs 的减少,因为这种细胞因子参与了外周 Tregs 的转化和维持。
OUA 在自身免疫性疾病、过敏和癌症中的影响,以及 OUA 作为肿瘤治疗的一种治疗方法的潜在用途,仍需要更多的研究。