N-nitrosodimethylamine (NDMA) induced apoptosis dependent on Fas/FasL complex in human leukocytes

Human and Experimental Toxicology - Tập 38 Số 5 - Trang 578-587 - 2019
Agnieszka Iwaniuk1, Kamil Grubczak2, Wioletta Ratajczak–Wrona1, Marzena Garley1, Karolina Nowak1, Ewa Jabłońska1
1Department of Immunology, Medical University of Białystok, Białystok, Poland
2Department of Regenerative Medicine and Immune Regulation, Medical University of Białystok, Białystok, Poland

Tóm tắt

Objective:To investigate the mechanism of apoptosis dependent on the Fas/FasL (Fas ligand) complex in the presence of N-nitrosodimethylamine (NDMA) in human leukocytes.Methods:Polymorphonuclear neutrophils (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated form whole blood by density centrifugation. The concentration of NDMA was assessed by cellular toxicity assay. Apoptotic cells were assessed with flow cytometry and the expression of pro- and antiapoptotic proteins was investigated by Western blotting in PMNs and PBMCs treated with NDMA and/or FasL.Results:PMNs showed a higher ratio of apoptotic cells than PBMCs after exposure to NDMA and/or FasL. Enhanced apoptosis was related to the increased expression of proapoptotic proteins in neutrophils following exposure to either NDMA or FasL. In PBMCs, the relation was observed after exposure to FasL only. PMNs and PBMCs incubated with NDMA and FasL simultaneously demonstrated the highest increase in protein expression.Conclusions:NDMA shows a stronger proapoptotic effect with PMNs than with PBMCs. The Fas/FasL complex, along with other proapoptotic proteins of the receptor (Fas, FADD) and mitochondrial pathway (Noxa, Puma, Bim), plays a key role in the induction of neutrophil apoptosis. Synergic effects of NDMA and FasL which lead to higher induction of apoptosis in PMNs than in PBMCs indicates a multistage and varied regulation of apoptosis in different populations of leukocytes.

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Thông tin xuất bản

Human and Experimental Toxicology

Tập 38 Số 5

578-587

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