Previous studies by Bruce Bochner and his colleagues at the Johns Hopkins Asthma and Allergy Center had zeroed in on the protein, Siglec-8, as an important player in allergic reactions. This protein is found on the surfaces of some types of immune cells, namely eosinophils, basophils and mast cells, which have diverse but cooperative roles in normal immune function and allergic diseases. Eosinophils directly combat foreign invaders, such as parasites. Basophils and mast cells store and release substances such as histamine, prostaglandins and cytokines, which signal other immune system cells to ready for battle.
When functioning correctly, these cells are a valuable aid to keeping the body healthy and infection-free. However, in allergic reactions and asthma attacks, the cells unleash an overwhelming response that typically harms the body more than it helps.
The researchers found in previous studies that when they activated Siglec-8 on the surface of eosinophils, the cells promptly died. Expecting the same suicidal response in mast cells, the scientists tested their theory in a new study on human mast cells and mast-cell-containing tissues.
Using mast cells grown in a lab, the researchers used antibodies to activate Siglec-8. “We were surprised to see that these cells just sat there happily in their petri dishes and lived on,” says Bochner, director of the Division of Allergy and Clinical Immunology at the Johns Hopkins University School of Medicine.
With their initial theory disproven, Bochner and his colleagues suspected that Siglec-8 might be slowing down other cellular processes based on the protein’s distinctive structure. To investigate what else Siglec-8 might inhibit, the scientists activated the protein in mast cells once again with antibodies. Then, they attempted to trigger an allergic response from these cells.
Normally, mast cells respond with an outpouring of histamine, prostaglandins and other substances that spur allergic reactions in other cells. However, Bochner and his colleagues found that cells with activated Siglec-8 released less than half the typical amount of these substances.
Extending their experiment from cells to whole tissues, Bochner and his colleagues used antibodies to activate mast cells’ Siglec-8 in small pieces of human lung saved from autopsies. When the researchers triggered the cells to release their payloads-an act that typically causes airways to sharply constrict-the contractions were about 25 percent weaker than in lung tissue where the mast cells’ Siglec-8 wasn’t activated.
The researchers are still unsure exactly how Siglec-8 inhibits mast cells from releasing their immune-triggering chemicals. However, follow-up experiments suggested that activating the protein keeps calcium from moving efficiently into the cells. Mast cells need this calcium signal to release their contents.
Bochner notes that researchers might eventually use these results, published in the February Journal of Allergy and Clinical Immunology, to develop a drug with this same effect. Such a drug would have the dual effect of blocking or reducing allergic reactions by killing eosinophils and preventing mast cells from releasing their substances.
“Both of these effects could make allergic diseases and asthma less severe,” he says. “It’s an intriguing approach because there are no drugs that specifically target both these cell types.”
Though drugs exist that affect either eosinophils or mast cells, Bochner says developing a single drug that takes aim at both types of cells could be even more effective than existing therapies and may also have a reduced risk of side effects. He and his colleagues are also searching for natural molecules in the body that activate Siglec-8, which could bring researchers a step closer to developing pharmaceuticals that target this protein.
Christen Brownlee | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy