Scientists working with Professor Bernd Kaina of the Institute of Toxicology at the Medical Center of Johannes Gutenberg University Mainz have demonstrated for the first time that certain cells circulating in human blood – so-called monocytes – are extremely sensitive to reactive oxygen species (ROS).
They were also able to clarify the reason for this: ROS are aggressive forms of oxygen that are generated during states of "oxidative stress" and play a significant role in various diseases. However, ROS are also naturally produced by cells of the immune system, in particular by macrophages, in response to exposure to pathogens.
Macrophages are, similar to dendritic cells, generated by monocytes, which happens when monocytes leave the blood stream and enter the tissue. The scientists show that both macrophages and dendritic cells are resistant to ROS, as opposed to their precursor cells, the monocytes.
The Mainz team attributes this hypersensitivity of monocytes to multiple defects in DNA repair that are apparent in these cells. They assume that a sophisticated mechanism for regulating the immune response and preventing excessive ROS production is behind this phenomenon, which was observed for the very first time. Their work has been published in the leading scientific journal Proceedings of the National Academy of Sciences.
It is generally known that one of the undesirable effects of ionizing radiation and drugs used to treat cancer is an impairment of the immune system, which ceases to function properly. However, it is still unclear which immune system cells respond most sensitively following radio- and chemotherapy, and which cells are resistant. "This is the question we addressed in our current research project," explains Professor Dr. Bernd Kaina, Director of the Institute of Toxicology at the University Medical Center in Mainz. "We were able to demonstrate that human monocytes are hypersensitive to reactive oxygen species (ROS), while macrophages 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."
Petra Giegerich | idw
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences