Sung C P, Arleth A J, Feuerstein G Z
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Circ Res. 1991 Jan;68(1):314-8. doi: 10.1161/01.res.68.1.314.
The nervous system and the autonomic system in particular have been associated with stress-induced changes in host resistance to infections and inflammatory reactions. Since a key step in initiation of inflammation is adhesion of leukocytes to the endothelium, we hypothesized that neuron-derived factors might be involved in this process. Neuropeptide Y (NPY), a 36-amino acid neuropeptide that is colocalized and released with norepinephrine from sympathetic nerves, has already been implicated in inflammatory reactions via modulation of histamine release from mast cells. This study was undertaken to examine the potential role of NPY in proinflammatory processes via modulation of endothelium-leukocyte interaction. NPY (0.01-10 microM) increased the adhesion of 51Cr-labeled human neutrophils or the human monocytic U937 cell line to human umbilical vein endothelial cells in a dose- and time-dependent manner. The stimulation of human umbilical vein endothelial cell adhesiveness occurred as early as 30 minutes and lasted over 48 hours. The increase of leukocyte adhesion to human umbilical vein endothelial cells by NPY was not inhibited by protein synthesis inhibitor cycloheximide, nor was it associated with expression of intercellular adhesion molecule-1 on human umbilical vein endothelial cells; in contrast, strong expression of intercellular adhesion molecule-1 was induced by tumor necrosis factor alpha and lipopolysaccharide endotoxin. These data suggest that neuron-derived factors such as NPY may serve as modulators of not only the neuromuscular unit but also the interaction of endothelial cells with leukocytes. In this capacity, the sympathetic nervous system might play an important role in the regulation of proaggregatory and hemostatic activity of microvessels.
神经系统，尤其是自主神经系统，与应激诱导的宿主抗感染能力变化及炎症反应有关。由于炎症起始的关键步骤是白细胞与内皮细胞的黏附，我们推测神经元衍生因子可能参与了这一过程。神经肽Y（NPY）是一种由36个氨基酸组成的神经肽，与去甲肾上腺素共同定位于交感神经并从交感神经释放，它已被证实可通过调节肥大细胞释放组胺而参与炎症反应。本研究旨在通过调节内皮细胞与白细胞的相互作用，探讨NPY在促炎过程中的潜在作用。NPY（0.01 - 10 microM）以剂量和时间依赖性方式增加了51Cr标记的人中性粒细胞或人单核细胞U937细胞系与人脐静脉内皮细胞的黏附。人脐静脉内皮细胞黏附性的刺激最早在30分钟时出现，并持续超过48小时。NPY增加白细胞与人脐静脉内皮细胞的黏附作用不受蛋白质合成抑制剂环己酰亚胺的抑制，也与人脐静脉内皮细胞上细胞间黏附分子-1的表达无关；相反，肿瘤坏死因子α和脂多糖内毒素可诱导细胞间黏附分子-1的强烈表达。这些数据表明，诸如NPY等神经元衍生因子不仅可能作为神经肌肉单位的调节剂，还可能作为内皮细胞与白细胞相互作用的调节剂。交感神经系统可能在微血管的促聚集和止血活性调节中发挥重要作用。
