Malendowicz L K, Macchi V, Brelinska R, Trejer M, Gottardo G, Nussdorfer G G
Department of Histology and Embryology, School of Medicine, Poznan, Poland.
Histol Histopathol. 1998 Jul;13(3):721-5. doi: 10.14670/HH-13.721.
Endothelins (ETs) are a family of vasoactive peptides widely distributed in the body systems, where they exert pleiotropic biological effects, acting through two main subtypes of receptors, named ETA and ETB. Evidence indicates that ET-1 plays a permissive role in the development of neural crest-derived structures, among which are the epithelial cells of the thymus. These cells are known to control proliferation and differentiation of thymocytes, a process requiring adequate levels of glucocorticoids. Therefore, we have investigated the effects of ET-1, that binds both ETA and ETB receptors, on thymocyte proliferation in monolaterally adrenalectomized rats with contralateral enucleated adrenal at day 4 and 8 of regeneration, when glucocorticoid production is very low and, respectively, rather normal. Metaphase index (percentage of metaphase arrested cells) of thymocytes is the lowest at day 4 of regeneration, and markedly rose at day 8, thereby confirming the need of sizable levels of circulating glucocorticoid for the maintenance of a normal rate of thymocyte proliferation. ET-1 markedly increased the mitotic index of thymocytes at both times of adrenal regeneration. At day 8 of regeneration, the ETA-receptor antagonist BQ-123 markedly lowered mitotic index of thymocytes, and annulled its ET-1-evoked raise. Conversely, the ETB-receptor antagonist BQ-788 was ineffective. Collectively, these findings clearly indicate that endogenous ETs, through the activation of ETA receptors, are involved in the maintenance and stimulation of thymocyte proliferation in the adult rat, thereby playing a possibly important role in the modulation of the immune-system functions.
内皮素（ETs）是一族血管活性肽，广泛分布于身体各系统，通过两种主要的受体亚型ETA和ETB发挥多效性生物学作用。有证据表明，ET-1在神经嵴衍生结构的发育中起允许作用，胸腺上皮细胞就属于这些结构。已知这些细胞控制胸腺细胞的增殖和分化，这一过程需要足够水平的糖皮质激素。因此，我们研究了能同时结合ETA和ETB受体的ET-1对单侧肾上腺切除且对侧肾上腺摘除的大鼠在再生第4天和第8天胸腺细胞增殖的影响，此时糖皮质激素分泌分别非常低和基本正常。胸腺细胞的中期指数（处于中期停滞的细胞百分比）在再生第4天最低，在第8天显著上升，从而证实维持正常胸腺细胞增殖速率需要相当水平的循环糖皮质激素。在肾上腺再生的两个时间点，ET-1均显著增加了胸腺细胞的有丝分裂指数。在再生第8天，ETA受体拮抗剂BQ-123显著降低了胸腺细胞的有丝分裂指数，并消除了ET-1引起的升高。相反，ETB受体拮抗剂BQ-788无效。总体而言，这些发现清楚地表明，内源性ETs通过激活ETA受体参与成年大鼠胸腺细胞增殖的维持和刺激，从而可能在免疫系统功能调节中发挥重要作用。
