Cunningham M E, Huribal M, Bala R J, McMillen M A
Department of Surgery, Bridgeport Hospital, CT, USA.
Crit Care Med. 1997 Jun;25(6):958-64. doi: 10.1097/00003246-199706000-00011.
To determine the effect of endothelin-1 and endothelin-4 on human monocyte production of cytokines.
Previous work from our laboratory has shown that endothelin-1 activates leukocytes. Endothelin-1 and endothelin-3 are principally produced by vascular endothelium. However, epidermal cells in gut mucosa, lung, and kidney produce endothelin-2 and endothelin-4, which differ by a single amino acid. While structurally similar to endothelin-1, endothelin-2 and endothelin-4 may affect gut smooth muscle and other tissues differently. The effect of endothelin-1 and endothelin-4 was examined on monocyte production of interleukins (IL) and neutrophil activation factors.
A clinically-oriented basic science laboratory in a Veterans Administration Hospital and Medical Center.
Healthy volunteer adult male/female medical students, researchers, and hospital workers.
Human peripheral blood mononuclear cells were separated on density gradients and cultured in media, with or without the addition of bacterial endotoxin or varying molar concentrations of endothelin-1 and endothelin-4. Supernatants were harvested at 10 mins, and at 1, 6, 12, 24, and 48 hrs, and enzyme-linked immunosorbent assays were performed to determine the presence of tumor necrosis factor-alpha, IL-1 beta, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor.
Endothelin-1 and endothelin-4 were potent stimuli for monocyte production of tumor necrosis factor-alpha, IL-8, and granulocyte-macrophage colony-stimulating factor. They also caused IL-1 beta and IL-6 production.
Endothelin-1 and endothelin-4 may activate leukocytes after shock or gut ischemia, resulting in further injury to reperfused tissues and distant injury to lungs and other organs.
确定内皮素 -1 和内皮素 -4 对人单核细胞细胞因子产生的影响。
我们实验室先前的研究表明内皮素 -1 可激活白细胞。内皮素 -1 和内皮素 -3 主要由血管内皮产生。然而，肠道黏膜、肺和肾中的表皮细胞可产生内皮素 -2 和内皮素 -4，它们仅相差一个氨基酸。虽然内皮素 -2 和内皮素 -4 在结构上与内皮素 -1 相似，但它们对肠道平滑肌和其他组织的影响可能不同。研究了内皮素 -1 和内皮素 -4 对单核细胞白细胞介素（IL）产生及中性粒细胞激活因子的影响。
一家退伍军人管理局医院及医疗中心的临床导向基础科学实验室。
健康志愿者成年男女医学生、研究人员及医院工作人员。
通过密度梯度分离人外周血单个核细胞，并在添加或不添加细菌内毒素或不同摩尔浓度内皮素 -1 和内皮素 -4 的培养基中培养。在 10 分钟、1 小时、6 小时、12 小时、24 小时和 48 小时收集上清液，进行酶联免疫吸附测定以确定肿瘤坏死因子 -α、IL -1β、IL -6、IL -8 和粒细胞 - 巨噬细胞集落刺激因子的存在。
内皮素 -1 和内皮素 -4 是单核细胞产生肿瘤坏死因子 -α、IL -8 和粒细胞 - 巨噬细胞集落刺激因子的强效刺激物。它们还可引起 IL -1β 和 IL -6 的产生。
内皮素 -1 和内皮素 -4 可能在休克或肠道缺血后激活白细胞，导致再灌注组织进一步损伤以及肺部和其他器官的远处损伤。
