Sookhai S, Wang J H, Winter D, Power C, Kirwan W, Redmond H P
Department of Academic Surgery, Cork University Hospital and University College Cork, Ireland.
Shock. 2000 Sep;14(3):295-9. doi: 10.1097/00024382-200014030-00009.
Activated neutrophil (PMN) adherence to vascular endothelium comprises a key step for both transendothelial migration and initiation of potentially deleterious release of PMN products. The biogenic amine, dopamine (DA), has been used for several decades in patients to maintain hemodynamic stability. The effect of dopamine on PMN transendothelial migration and adhesion receptor expression and on the endothelial molecules, E-selectin and ICAM-1, was evaluated. PMN were isolated from healthy controls, stimulated with lipopolysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) and treated with dopamine. CD 11b and CD 18 PMN adhesion receptor expression were assessed flow cytometrically. In a separate experiment, the chemoattractant peptide, IL-8, was placed in the lower chamber of transwells, and PMN migration was assessed. Human umbilical vein endothelial cells (HUVEC) were stimulated with LPS/TNF-alpha and incubated with dopamine. ICAM-1 and E-selectin endothelial molecule expression were assessed flow cytometrically. There was a significant increase in transendothelial migration in stimulated PMN compared with normal PMN (40 vs. 14%, P < 0.001). In addition, PMN CD11b/CD18 was significantly upregulated in stimulated PMN compared with normal PMN (252.4/352.4 vs. 76.7/139.4, P < 0.001) as were endothelial E-selectin/ICAM-1 expression compared with normal EC (8.1/9 vs. 3.9/3.8, P < 0.05). After treatment with dopamine, PMN transmigration was significantly decreased compared with stimulated PMN (8% vs. 40%, P < 0.001). Furthermore, dopamine also attenuated PMN CD11b/CD18 and the endothelial molecules E-selectin and ICAM-1 compared with stimulated PMN/EC that were not treated dopamine (174/240 vs. 252/352, P < 0.05 and 4/4.4 vs. 8.1/9, P < 0.05. respectively). The chemoattractant effect of IL-8 was also attenuated. These results identify for the first time that dopamine attenuates the initial interaction between PMN and the endothelium, and consequently, modulates PMN exudation. Thus, biogenic amines, including dopamine, may function as anti-inflammatory cytokines.
活化的中性粒细胞（PMN）黏附于血管内皮是跨内皮迁移以及启动PMN产物潜在有害释放的关键步骤。生物胺多巴胺（DA）已在患者中使用数十年以维持血流动力学稳定。评估了多巴胺对PMN跨内皮迁移、黏附受体表达以及对内皮分子E选择素和细胞间黏附分子-1（ICAM-1）的影响。从健康对照中分离PMN，用脂多糖（LPS）和肿瘤坏死因子-α（TNF-α）刺激，并使用多巴胺处理。通过流式细胞术评估CD11b和CD18 PMN黏附受体表达。在另一个实验中，将趋化肽白细胞介素-8（IL-8）置于Transwell小室的下室中，并评估PMN迁移。用人脐静脉内皮细胞（HUVEC）用LPS/TNF-α刺激并与多巴胺孵育。通过流式细胞术评估ICAM-1和E选择素内皮分子表达。与正常PMN相比，刺激后的PMN跨内皮迁移显著增加（40%对14%，P<0.001）。此外，与正常PMN相比，刺激后的PMN中PMN CD11b/CD18显著上调（252.4/352.4对76.7/139.4，P<0.001），与正常内皮细胞相比，内皮E选择素/ICAM-1表达也上调（8.1/9对3.9/3.8，P<0.05）。用多巴胺处理后，与刺激后的PMN相比，PMN跨膜迁移显著降低（8%对40%，P<0.001）。此外，与未用多巴胺处理的刺激后的PMN/内皮细胞相比，多巴胺还减弱了PMN CD11b/CD18以及内皮分子E选择素和ICAM-1（分别为174/240对252/352，P<0.05和4/4.4对8.1/9，P<0.05）。IL-8的趋化作用也减弱。这些结果首次表明多巴胺减弱了PMN与内皮之间的初始相互作用，因此调节了PMN渗出。因此，包括多巴胺在内的生物胺可能起到抗炎细胞因子的作用。
