Jabłonski Jakub, Jabłonska Ewa, Moniuszko-Jakoniuk Janina
Department of Toxicology, Medical University of Białystok, Białystok, Poland.
Immunopharmacol Immunotoxicol. 2007;29(2):287-96. doi: 10.1080/08923970701513021.
The intracellular mechanisms of NDMA-induced apoptosis of neutrophils have not yet been fully understood. The aim of this study was to explain whether the TRAIL/DR5 system is implicated in NDMA-induced apoptosis of human neutrophils. The expression of TRAIL and DR5 was examined, as well as the secretion of sTRAIL and sDR5 by human neutrophils treated with NDMA confronted with intensity apoptosis of these cells. For comparative purposes similar examinations in autologous peripheral blood mononuclear cells (PBMC) were performed. Decreased expression and secretion of TRAIL and increased expression and secretion of DR5 associated with increased intensity of apoptosis of polymorphonuclear leukocytes (PMNs) suggest that NDMA-induced apoptosis in these cells may be depend on TRAIL/DR5 system. Autologous PBMCs no exerted that changes in the expression and secretion of TRAIL as well as in the intensity of apoptosis. However, the expression and secretion of DR5 by PBMCs were similar to those by PMNs. Differences above suggest that PMNs are more sensitive to unfavorable action of NDMA than PBMCs.
N-二甲基亚硝胺（NDMA）诱导中性粒细胞凋亡的细胞内机制尚未完全阐明。本研究旨在探讨肿瘤坏死因子相关凋亡诱导配体（TRAIL）/死亡受体5（DR5）系统是否参与NDMA诱导的人中性粒细胞凋亡。检测了TRAIL和DR5的表达，以及经NDMA处理的人中性粒细胞在发生强烈凋亡时sTRAIL和sDR5的分泌情况。为作比较，对自体外周血单个核细胞（PBMC）进行了类似检测。随着多形核白细胞（PMN）凋亡强度增加，TRAIL表达和分泌减少，DR5表达和分泌增加，提示NDMA诱导这些细胞凋亡可能依赖TRAIL/DR5系统。自体PBMC未出现TRAIL表达和分泌以及凋亡强度的变化。然而，PBMC中DR5的表达和分泌与PMN相似。上述差异表明，PMN比PBMC对NDMA的不利作用更敏感。
