Mohamed Hager, Gebski Eric, Reyes Rufranshell, Beane Samuel, Wigdahl Brian, Krebs Fred C, Stapelmann Katharina, Miller Vandana
Department of Microbiology and Immunology, and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Department of Biology, College of Arts and Sciences, Drexel University, Philadelphia, PA 19104, USA.
Cancers (Basel). 2021 May 18;13(10):2437. doi: 10.3390/cancers13102437.
Non-thermal plasma application to cancer cells is known to induce oxidative stress, cytotoxicity and indirect immunostimulatory effects on antigen presenting cells (APCs). The purpose of this study was to evaluate the responses of two leukemic cell lines-Jurkat T lymphocytes and THP-1 monocytes-to NTP-generated reactive oxygen and nitrogen species (RONS). Both cell types depleted hydrogen peroxide, but THP-1 cells neutralized it almost immediately. Jurkat cells transiently blunted the frequency-dependent increase in nitrite concentrations in contrast to THP-1 cells, which exhibited no immediate effect. A direct relationship between frequency-dependent cytotoxicity and mitochondrial superoxide was observed only in Jurkat cells. Jurkat cells were very responsive to NTP in their display of calreticulin and heat shock proteins 70 and 90. In contrast, THP-1 cells were minimally responsive or unresponsive. Despite no NTP-dependent decrease in cell surface display of CD47 in either cell line, both cell types induced migration of and phagocytosis by APCs. Our results demonstrate that cells modulate the RONS-mediated changes in liquid chemistry, and, importantly, the resultant immunomodulatory effects of NTP can be independent of NTP-induced cytotoxicity.
已知非热等离子体作用于癌细胞可诱导氧化应激、细胞毒性以及对抗抗原呈递细胞（APC）的间接免疫刺激作用。本研究的目的是评估两种白血病细胞系——Jurkat T淋巴细胞和THP-1单核细胞——对非热等离子体产生的活性氧和氮物种（RONS）的反应。两种细胞类型均消耗过氧化氢，但THP-1细胞几乎立即将其中和。与THP-1细胞不同，Jurkat细胞瞬时减弱了亚硝酸盐浓度随频率的增加，THP-1细胞未表现出即时效应。仅在Jurkat细胞中观察到了频率依赖性细胞毒性与线粒体超氧化物之间的直接关系。Jurkat细胞在钙网蛋白以及热休克蛋白70和90的表达方面对非热等离子体反应非常敏感。相比之下，THP-1细胞反应极小或无反应。尽管两种细胞系中均未出现非热等离子体依赖性的CD47细胞表面表达降低，但两种细胞类型均诱导了APC的迁移和吞噬作用。我们的结果表明，细胞可调节RONS介导的液体化学变化，重要的是，非热等离子体产生的免疫调节作用可能独立于非热等离子体诱导的细胞毒性。
