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Human immune cells react sensitively to 'stress'
Date:2/2/2012

ges and dendritic cells derived from monocytes by cytokine maturation are resistant." The scientists observed this extreme sensitivity of monocytes after exposure to radiation, chemicals, and even oxidized low-density lipoprotein (oxLDL), which plays a role in atherosclerosis. All of the above resulted in the formation of intracellular ROS, which damages the DNA and leads to cell death or even malignant transformation. Specific immune system cells, particularly the macrophages, produce ROS in response to an invasion of the body by pathogens. Ideally, production of ROS should cease once the pathogens have been eliminated. There also need to be limitations on the quantity of ROS produced, as these can damage healthy cells in inflamed tissue as well. In fact, chronic infections, in which ROS are continuously being produced, are frequently linked to an increased susceptibility to cancer.

Why do monocytes react so sensitively to ROS? Kaina's team has successfully determined the cause of the hypersensitivity of monocytes to oxidative stress: The monocytes were unable to repair DNA following ROS-induced damage to their genetic substance. This is because these cells produce very low levels of certain important repair proteins called XRCC1, ligase III, PARP-1, and DNA-PK in medical jargon. "Monocytes are in fact defective as far as two important DNA repair systems are concerned, i.e. base excision repair and DNA double-strand break repair," explains Kaina. "Thus far, a general repair defect of this nature has been observed neither in the cells of the human body nor in experimental in vitro systems."

Professor Kaina assumes that the repair defect in monocytes plays an important role in the regulation of the immune response: To prevent excessive production of ROS by macrophages in the inflamed tissue and an overactivation of the immune response, monocytes, as precursor cells of the ROS-producing macrophages, undergo increased and selective destruction due t
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Contact: Professor Dr. Bernd Kaina
kaina@uni-mainz.de
49-613-117-9217
Johannes Gutenberg Universitaet Mainz
Source:Eurekalert

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