Blum A M, Metwali A, Mathew R C, Cook G, Elliott D, Weinstock J V
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
J Immunol. 1992 Dec 1;149(11):3621-6.
The granulomas of mice infected with Schistosoma mansoni for 8 wk have macrophages that secrete somatostatin 1-14 (SOM). Within the granuloma, SOM has no known function. To uncover the possible significance of SOM produced within this granulomatous inflammation, we sought SOM receptors on distinct cellular components of the granuloma to identify cells targeted for SOM action. [125I]SOM 1-14 bound to dispersed granuloma inflammatory cells specifically and reversibly. Scatchard analysis suggested one receptor type (kDa 4.28 x 10(-9) M). Octreotide, a stable SOM derivative, displaced radioligand (kDa 1.01 x 10(-10) M), but SOM 1-28, substance P, and vasoactive intestinal peptide did not. The SOM receptor localized exclusively to a subset of granuloma CD4+ T lymphocytes. Using IL-5 and IFN-gamma ELISA, it was shown that granuloma T cells can secrete appreciable IL-5 and IFN-gamma when stimulated with Ag or mitogen. Both SOM and octreotide at concentrations as low as 10(-10) M substantially decreased IFN-gamma secretion from Ag or mitogen-stimulated T cells, but at concentrations as high as 10(-6) did not affect IL-5 production. Octreotide administered to animals in vivo decreased the intensity of the granulomatous response. Thus, some granuloma T cells have SOM 1-14 receptors. SOM 1-14, a product of granuloma macrophages, may participate in regulation of the granulomatous response by modulating the secretion of some lymphokines. Octreotide, a clinically useful SOM analog, mimics the action of SOM on the immune system.
感染曼氏血吸虫8周的小鼠肉芽肿中有分泌生长抑素1 - 14（SOM）的巨噬细胞。在肉芽肿内，SOM的功能尚不清楚。为了揭示在这种肉芽肿性炎症中产生的SOM的潜在意义，我们在肉芽肿的不同细胞成分上寻找SOM受体，以确定SOM作用的靶细胞。[125I]SOM 1 - 14特异性且可逆地结合到分散的肉芽肿炎症细胞上。Scatchard分析提示存在一种受体类型（解离常数为4.28×10⁻⁹ M）。奥曲肽，一种稳定的SOM衍生物，能取代放射性配体（解离常数为1.01×10⁻¹⁰ M），但SOM 1 - 28、P物质和血管活性肠肽则不能。SOM受体仅定位于肉芽肿CD4⁺ T淋巴细胞的一个亚群。使用IL - 5和IFN - γ ELISA检测发现，当用抗原或丝裂原刺激时，肉芽肿T细胞能分泌可观的IL - 5和IFN - γ。低至10⁻¹⁰ M浓度的SOM和奥曲肽均可显著降低抗原或丝裂原刺激的T细胞分泌IFN - γ，但高达10⁻⁶ M浓度时对IL - 5的产生没有影响。给动物体内注射奥曲肽可降低肉芽肿反应的强度。因此，一些肉芽肿T细胞具有SOM 1 - 14受体。肉芽肿巨噬细胞产生的SOM 1 - 14可能通过调节某些淋巴因子的分泌参与肉芽肿反应的调节。奥曲肽，一种临床有用的SOM类似物，模拟了SOM对免疫系统的作用。
