Cioca D P, Watanabe N, Isobe M
Department of Internal Medicine, Shinshu University School of Medicine, Nagano, Japan.
Jpn Heart J. 2000 May;41(3):385-98. doi: 10.1536/jhj.41.385.
We explored the mechanism through which patients sometimes show immunosuppression after cardiac surgery. To test the hypothesis that commonly used drugs could cause apoptosis of immune cells, the proapoptotic effects of heparin and catecholamines (dopamine and dobutamine) on peripheral blood lymphocytes were evaluated. Peripheral blood lymphocytes were purified from blood samples of normal healthy volunteers. These cells were cultured in the presence of heparin, dobutamine or dopamine. The apoptosis was quantified by Annexin V fluorescent assay, by DNA content and by morphological assessment. Lymphocytes did not show significant levels of apoptosis induction after 24 hours of incubation with heparin. Both dopamine and dobutamine demonstrated a clear apoptosis inducing effect on lymphocytic population after 24 and 48 hours of culture, in concentrations comparable with the clinically used levels. Apoptosis was time and concentration dependent for both catecholamines. The dopamine and dobutamine effect on lymphocyte viability was due, at least partially, to lymphocyte beta receptor engagement, as proved by blocking the receptor with propranolol. These results suggest that catecholamines could induce apoptosis of lymphocytes. This finding may be associated with immunosuppression observed in patients undergoing cardiac surgery.
我们探究了心脏手术后患者有时会出现免疫抑制的机制。为了验证常用药物可能导致免疫细胞凋亡这一假说,我们评估了肝素和儿茶酚胺(多巴胺和多巴酚丁胺)对外周血淋巴细胞的促凋亡作用。从正常健康志愿者的血样中纯化出外周血淋巴细胞。将这些细胞在肝素、多巴酚丁胺或多巴胺存在的情况下进行培养。通过膜联蛋白V荧光测定法、DNA含量测定法及形态学评估对细胞凋亡进行定量分析。用肝素孵育24小时后,淋巴细胞未表现出明显的凋亡诱导水平。在培养24小时和48小时后,多巴胺和多巴酚丁胺在与临床使用浓度相当的情况下,均对淋巴细胞群体表现出明显的凋亡诱导作用。两种儿茶酚胺的凋亡诱导作用均呈时间和浓度依赖性。用普萘洛尔阻断受体证明,多巴胺和多巴酚丁胺对淋巴细胞活力的影响至少部分是由于淋巴细胞β受体的激活。这些结果表明,儿茶酚胺可诱导淋巴细胞凋亡。这一发现可能与心脏手术患者中观察到的免疫抑制有关。