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
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy