The findings, to be published Sept. 2 in the online version of Nature Immunology, reveal that, in mice, mast cells help decrease skin damage over time from sun exposure or from poison oak.
"These reactions are much worse if mast cells aren't present," said senior author Stephen Galli, MD, professor and chair of pathology. He noted the insight may open new possibilities for the treatment of these problems.
The findings contradict mast cells' reputation for being the trigger-happy gunslinger in an allergic reaction. Located just beneath the skin and in the loose connective tissue throughout the body, mast cells lie in wait for intruders. Packed with granules containing inflammation-inciting molecules such as histamine, they sometimes also react to non-threatening trespassers, such as pollens or plant oils. These confrontations cause allergic reactions and, in extreme cases, the life-threatening overreaction of anaphylaxis seen in bee-sting or peanut allergies.
Mast cells also affect the severity of eczema and asthma, giving rise to some therapies that focus on counteracting their activity. "Some people say, 'Let's get rid of them,'" said Galli, who also holds the Mary Hewitt Loveless Professorship in the School of Medicine. "But we did not evolve mast cells just so we could eat a peanut and die."
Rather than characterize the mast cell as an agitator, Galli said it would be more aptly described by the title of a Clint Eastwood western. "The mast cell would have its good, bad and ugly sides - it would depend on the circumstance," he said. "In the end, I think you would be convinced it was mostly a good guy."
Galli's lab has shown mast cells can help corral rather than unleash distress. His team's previous research in 2006 found that mast cells help break down snake venom poison, and a study in 2004 revealed the cells helped mice survive severe bacterial infection.
The new research is the first to investigate long-term reactions by mast cells to poison oak and sun exposure. His team exposed the ears of mice to either cycles of ultraviolet radiation or urushiol, the irritating oil of poison oak. About a week later, mice genetically lacking mast cells showed much more inflammation than normal mice, and developed skin ulcers. Injections of mast cells helped reduce the ear swelling and prevent the ulceration. "All you have to do to cure the mice of this problem is put the mast cells back in," Galli said.
The discovery originated from an unintended observation by Michelle Grimbaldeston, PhD, first author and postdoctoral scholar in pathology. While similar studies have stopped following mouse reactions past the first 48 hours, she kept records for two weeks. "Just by chance I looked a bit farther along," said Grimbaldeston, who is also a C.J. Martin overseas biomedical fellow of the Australian National Health and Medical Research Council.
After just five days, she noticed the ears of mice lacking mast cells were surprisingly thicker than were the ears of normal mice, suggesting an accumulation of white blood cells. By injecting mast cells back into the deficient mice, Grimbaldeston found the immune-suppressing molecule the cells secrete to limit ear swelling: interleukin-10. She also identified which antibodies activated the mast cell receptors to trigger IL-10's release.
Trial injections of IL-10 have reduced inflammation in patients suffering from rheumatoid arthritis and psoriasis, with mixed results. Yet given the manufacturing cost of producing IL-10, Galli thinks it an unlikely practical treatment for poison oak or sun exposure.
The next studies will look into whether mast cells reduce the development of skin tumors, such as melanoma or carcinomas, from longer term ultraviolet exposure. The group will also investigate what other molecules contribute to suppressing the inflammation. "You can't explain all of the anti-inflammatory aspects of mast cells with IL-10," Galli said.
"The fact that one sees the mast cell playing a role in resolving inflammation is surprising," said Juan Rivera, PhD, chief of the molecular inflammation section of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study. Research has focused on how quickly mast cells unleash inflammation, Rivera said, rather than how they might mitigate it. "I think it is a very intriguing finding that the mast cell plays this dual role," he said.
Brian Lee | EurekAlert!
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
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...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
26.04.2017 | Materials Sciences
26.04.2017 | Agricultural and Forestry Science
26.04.2017 | Physics and Astronomy