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A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro
Published on: January 9, 2018
Glycation interferes with natural killer cell function
Philip Rosenstock1, Veronika Bezold1, Kaya Bork1
1Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystr. 1, D-06114, Halle/Saale, Germany.
Abstract:
One hallmark of molecular aging is glycation, better known as formation of so-called advanced glycation end products (AGEs), where reactive carbonyls react with amino-groups of proteins. AGEs accumulate over time and are responsible for various age-dependent diseases and impairments. Two very potent dicarbonyls to generate AGEs are glyoxal (GO) and methylglyoxal (MGO). The plasma level of such dicarbonyls is higher in aging and age-related diseases. Natural killer (NK) cells are cells of the innate immune system and provide a major defense against tumor cells and virus infected cells. They are able to kill modified or infected cells and produce different cytokines to modulate the function of other immune cells. Here we investigated the effect of GO- and MGO-induced glycation on the function of NK cells. Using the human NK cell line NK-92, we could demonstrate that both GO and MGO lead to glycation of cellular proteins, but that MGO interferes much stronger with NK cell function (cytotoxicity) than GO. In addition, glycation of NK cell targets, such as K562 tumor cells, also interferes with their lysis by NK cells. From this data we conclude that glycation acts negatively on NK cells function and reduces their cytotoxic potential towards tumor cells.
Insights
Advanced glycation end products (AGEs) impair natural killer (NK) cell function. Methylglyoxal (MGO) negatively impacts NK cell cytotoxicity more than glyoxal (GO), reducing tumor cell lysis.
Area of Science:
- Immunology
- Molecular Biology
- Aging Research
Background:
- Molecular aging is characterized by the accumulation of advanced glycation end products (AGEs).
- Reactive carbonyls like glyoxal (GO) and methylglyoxal (MGO) are key contributors to AGE formation.
- Elevated dicarbonyl levels are observed in aging and age-related diseases, impacting immune function.
Purpose of the Study:
- To investigate the impact of GO- and MGO-induced glycation on natural killer (NK) cell function.
- To assess the effects of glycation on NK cell cytotoxicity and cytokine production.
- To determine if glycation of target cells affects NK cell-mediated lysis.
Main Methods:
- Utilized the human NK cell line NK-92 for experimental analysis.
- Exposed NK cells and K562 tumor cells to glyoxal (GO) and methylglyoxal (MGO).
- Assessed NK cell protein glycation levels and functional parameters, including cytotoxicity.
Main Results:
- Both GO and MGO induced glycation of proteins in NK cells.
- Methylglyoxal (MGO) significantly impaired NK cell function and cytotoxicity compared to glyoxal (GO).
- Glycation of target tumor cells (K562) also reduced their susceptibility to NK cell lysis.
Conclusions:
- Glycation negatively affects NK cell function and cytotoxic potential.
- MGO poses a greater threat to NK cell-mediated anti-tumor immunity than GO.
- These findings highlight glycation as a detrimental factor in immune surveillance against cancer.
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