Acute Respiratory Distress Syndrome, or ARDS, is an often fatal complication of severe traumatic injury, bacterial infections, blood transfusions and overdoses of some medications. In ARDS, the lungs become swollen with fluid and breathing becomes impossible. Thirty percent to 40 percent of patients die. There is no effective treatment.
Sepsis, an overwhelming bacterial infection of the blood and organs, is the most common cause of ARDS. When the immune system responds to the infection, molecules called inflammatory cytokines and chemokines are released. These molecules attract inflammatory white blood cells and destroy bacteria, but also lead to fever, swelling and other symptoms of shock and can wreak havoc on the patient in the course of fighting off the infection.
"Without an inflammatory response, bacterial invaders in the lungs can kill, but too intense a response can also be fatal," said Kurt Bachmaier, UIC research assistant professor in pharmacology and first author of the study. "We need a better understanding of how the immune system modulates this defense so that we can understand what goes wrong in life-threatening lung failure."
The researchers created a mouse model that lacks the gene for a protein, called Cblb, which was known to play a crucial role in chronic inflammation and auto-immunity through regulation of T- and B-cells.
When sepsis was induced in mice with and without the Cblb gene, there was a marked difference in the level of the inflammatory response and survival. Mice lacking the Cblb gene were much less likely to survive than control mice.
The UIC researchers were able to show how Cblb regulates the immune response. They showed that in normal mice, a receptor found in lung tissue that induces the release of inflammatory cytokines and chemokines disappears from the cell surface after about an hour, ending the signaling of the immune response.
In the Cblb-deficient mice the receptor stays on the surface, and the inflammatory response is not turned off.
The researchers were also able to show that a protein that controls the production of inflammatory cytokines, called NF-kB, is induced in lung tissue after sepsis by that receptor to a much greater extent from the Cblb-deficient mice than in normal mice. NF-kB is known to induce swelling of tissues.
"There are already early-stage drug trials of treatments for ARDS targeting NF-kB," said Bachmaier. "This discovery has real clinical implications in the treatment and prevention of life-threatening lung failure."
Cblb is a potential drug target that may lead to a new class of anti-bacterial drugs, says Dr. Asrar Malik, distinguished professor and head of pharmacology and a senior author on the paper. Malik and Bachmaier have recently filed a patent on the basis of these findings.
Jeanne Galatzer-Levy | EurekAlert!
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy