Ferone D, van Hagen P M, Colao A, Annunziato L, Lamberts S W, Hofland L J
Department of Internal Medicine III, Erasmus University, Rotterdam, The Netherlands.
Ann Med. 1999 Oct;31 Suppl 2:28-33.
The thymus is the primary lymphoid organ where different factors participate in regulating the proliferation and differentiation of T cells. The thymic epithelium is the main cellular component in driving the maturation of thymocytes through cell-to-cell and extracellular matrix-mediated interactions. Thymic hormones and cytokines play a critical role in the proliferation, differentiation and selection of precursor cells along the T-cell lineage. However, other locally produced hormones and neuropeptides participate in thymic functions in an autocrine and paracrine manner. Some of them have well-characterized actions, whereas somatostatin (SS), although it has been identified, has not been investigated in detail. SS inhibits hormone and exocrine secretion, modulates neurotransmission and inhibits cell proliferation. The biological effects of SS are mediated through five G protein-coupled membrane receptor subtypes (sst1-5). SS receptors (SS-R) have been demonstrated in normal tissues and tumours at the protein and mRNA levels. Sst2 mRNA has been detected in the murine thymus, whereas sst3 and sst4 mRNAs are expressed in the rat immune system. The significance of the presence of specific SS-R subtypes remains to be clarified. Moreover, the activation of lymphoid cells seems to modify their SS-R expression pattern. SS, sst1, sst2A and sst3 mRNAs have been found in normal human thymic tissue, whereas enriched cultured thymic epithelial cells (TEC) selectively express SS, sst1 and sst2A mRNAs. Furthermore, TEC respond in vitro to SS and octreotide by inhibiting cell proliferation. Immunoreactivity for sst2A has been detected primarily in the medulla, where TEC, dendritic cells and macrophages are the major components, in line with the predominant binding of the sst2 receptor-preferring ligand [125I-Tyr3]-octreotide in this region. The heterogeneous distribution of SS-R subtypes on specific cell subsets indicates that SS may play a paracrine and/or autocrine role in regulating cell activities in the thymus.
胸腺是主要的淋巴器官,不同因素参与调节T细胞的增殖和分化。胸腺上皮是通过细胞间和细胞外基质介导的相互作用驱动胸腺细胞成熟的主要细胞成分。胸腺激素和细胞因子在T细胞谱系前体细胞的增殖、分化和选择中起关键作用。然而,其他局部产生的激素和神经肽以自分泌和旁分泌方式参与胸腺功能。其中一些具有明确的作用,而生长抑素(SS)虽然已被鉴定,但尚未进行详细研究。SS抑制激素和外分泌分泌,调节神经传递并抑制细胞增殖。SS的生物学效应通过五种G蛋白偶联膜受体亚型(sst1 - 5)介导。SS受体(SS - R)已在正常组织和肿瘤中在蛋白质和mRNA水平得到证实。在小鼠胸腺中检测到sst2 mRNA,而sst3和sst4 mRNA在大鼠免疫系统中表达。特定SS - R亚型存在的意义仍有待阐明。此外,淋巴细胞的激活似乎会改变其SS - R表达模式。在正常人胸腺组织中发现了SS、sst1、sst2A和sst3 mRNA,而富集培养的胸腺上皮细胞(TEC)选择性表达SS、sst1和sst2A mRNA。此外,TEC在体外对SS和奥曲肽有反应,通过抑制细胞增殖。主要在髓质中检测到sst2A的免疫反应性,其中TEC、树突状细胞和巨噬细胞是主要成分,这与该区域sst2受体偏好配体[125I - Tyr3] - 奥曲肽的主要结合情况一致。SS - R亚型在特定细胞亚群上的异质性分布表明,SS可能在调节胸腺细胞活动中发挥旁分泌和/或自分泌作用。