Leszczynski D, Josephs M D, Fournier R S, Foegh M L
Department of Surgery, Georgetown University Medical Center, Washington, DC.
Regul Pept. 1993 Feb 18;43(3):131-40. doi: 10.1016/0167-0115(93)90147-z.
The effect of angiopeptin, a stable analogue of somatostatin, was studied on basal and interleukin-1-beta-induced endothelial cell adhesiveness for mononuclear cells, and compared to the effect of somatostatin. Angiopeptin and somatostatin decreased basal and interleukin-1-beta-induced endothelial cell adhesiveness for mononuclear cells. The decreased mononuclear cells adhesion to endothelial cells exposed to angiopeptin and somatostatin is not due to modulation of the expression of intrecellular adhesion molecule-1 because neither angiopeptin nor somatostatin decreased basal and interleukin-1-beta-induced expression of this adhesion molecule. The effect of angiopeptin in inhibiting endothelial cell adhesiveness for mononuclear cells was abolished by addition of dibutyryl-cyclic AMP. Angiopeptin induced a transient decrease in basal and interleukin-1-beta-induced cyclic AMP levels in endothelial cells. Exposure of unstimulated and interleukin-1-beta-activated endothelial cells to KT5720, a specific inhibitor of cyclic AMP-dependent protein kinase, decreased endothelial cell adhesiveness for mononuclear cells. Thus, angiopeptin most likely diminishes endothelial adhesiveness for mononuclear cells by affecting the cyclic AMP-dependent protein kinase signal transduction pathway. The findings suggest that angiopeptin and somatostatin may modify the development of the immune response by attenuating endothelial cell adhesiveness for mononuclear cells. Angiopeptin may have a potential clinical application as a modulator of some aspects of the immune response due to its long half-life and prolonged inhibitory effect on interleukin-1-beta induced endothelial adhesiveness for mononuclear cells.
研究了生长抑素的稳定类似物血管肽对基础状态及白细胞介素-1β诱导的内皮细胞与单核细胞黏附性的影响，并与生长抑素的作用进行了比较。血管肽和生长抑素均降低了基础状态及白细胞介素-1β诱导的内皮细胞与单核细胞的黏附性。单核细胞与暴露于血管肽和生长抑素的内皮细胞黏附性降低并非由于细胞间黏附分子-1表达的调节，因为血管肽和生长抑素均未降低基础状态及白细胞介素-1β诱导的该黏附分子的表达。添加二丁酰环磷腺苷可消除血管肽抑制内皮细胞与单核细胞黏附性的作用。血管肽可使内皮细胞基础状态及白细胞介素-1β诱导的环磷腺苷水平短暂降低。将未刺激及白细胞介素-1β激活的内皮细胞暴露于环磷腺苷依赖性蛋白激酶的特异性抑制剂KT5720，可降低内皮细胞与单核细胞的黏附性。因此，血管肽很可能通过影响环磷腺苷依赖性蛋白激酶信号转导途径来降低内皮细胞与单核细胞的黏附性。这些发现提示，血管肽和生长抑素可能通过减弱内皮细胞与单核细胞的黏附性来改变免疫反应的发展。由于血管肽半衰期长且对白细胞介素-1β诱导的内皮细胞与单核细胞黏附性具有持久的抑制作用，它可能作为免疫反应某些方面的调节剂具有潜在的临床应用价值。
