Elliott D E, Li J, Blum A M, Metwali A, Patel Y C, Weinstock J V
Department of Internal Medicine, Division of Gastroenterology-Hepatology, University of Iowa College of Medicine, Iowa City, USA.
Eur J Immunol. 1999 Aug;29(8):2454-63. doi: 10.1002/(SICI)1521-4141(199908)29:08<2454::AID-IMMU2454>3.0.CO;2-H.
Macrophages secrete the immunoregulatory peptide somatostatin (SOM) that inhibits IFN-gamma release by splenocytes and granuloma cells of schistosome-infected mice. In this report we demonstrate that granuloma cells express mRNA for the SOM receptor SSTR2 but not the other four SSTR subtypes. Blocking SSTR2 activity with anti-SSTR2 antiserum prevents SOM inhibition of T cell IFN-gamma production. This demonstrates that SOM regulates T cell function via SSTR2. Two isoforms of SSTR2 exist due to alternative RNA splicing. We developed sensitive and specific competitive PCR assays to quantify total SSTR2, SSTR2A and SSTR2B mRNA levels. The SSTR2A isoform accounts for 99% of inflammatory cell SSTR2 mRNA and does not appear to be regulated at the transcripitonal level. B cells and macrophage cell lines also express SSTR2 mRNA which raises the possibility that SOM influences T cell IFN-gamma release by regulating accessory cell function. We show that SOM acts directly on T cells to inhibit TCR-stimulated IFN-gamma release. Thus, SOM may directly regulate T cell IFN-gamma release at inflammatory sites.
巨噬细胞分泌免疫调节肽生长抑素（SOM），该物质可抑制血吸虫感染小鼠的脾细胞和肉芽肿细胞释放γ干扰素。在本报告中，我们证明肉芽肿细胞表达生长抑素受体SSTR2的mRNA，但不表达其他四种SSTR亚型的mRNA。用抗SSTR2抗血清阻断SSTR2活性可阻止SOM对T细胞γ干扰素产生的抑制作用。这表明SOM通过SSTR2调节T细胞功能。由于RNA可变剪接，存在两种SSTR2亚型。我们开发了灵敏且特异的竞争性PCR检测方法，以定量总SSTR2、SSTR2A和SSTR2B的mRNA水平。SSTR2A亚型占炎症细胞SSTR2 mRNA的99%，且在转录水平上似乎不受调控。B细胞和巨噬细胞系也表达SSTR2 mRNA，这增加了SOM通过调节辅助细胞功能影响T细胞γ干扰素释放的可能性。我们发现SOM直接作用于T细胞，抑制TCR刺激的γ干扰素释放。因此，SOM可能在炎症部位直接调节T细胞γ干扰素的释放。
