BOSTON In demonstrating that a group of calcium ion channels play a crucial role in triggering inflammatory responses, researchers at Beth Israel Deaconess Medical Center (BIDMC) have not only solved a longstanding molecular mystery regarding the onset of asthma and allergy symptoms, but have also provided a fundamental discovery regarding the functioning of mast cells. Their findings appear in the January 2008 issue of Nature Immunology.
A group of immune cells found in tissues throughout the body, mast cells were once exclusively known for their role in allergic reactions, according to the studys lead author Monika Vig, PhD, an investigator in the Department of Pathology at BIDMC and Instructor of Medicine at Harvard Medical School. Mast cells store inflammatory cytokines and compounds [including histamine and heparin] in sacs called granules, she explains. When the mast cells encounter an allergen pollen, for example they degranuate, releasing their contents and triggering allergic reactions.
But, she adds, in recent years, scientists have uncovered numerous other roles for mast cells, suggesting they are key to a number of biological processes and are involved in diseases ranging from multiple sclerosis and rheumatoid arthritis to cancer and atherosclerosis.
In order for mast cells to function, they require a biological signal specifically, calcium. Calcium moves in and out of the cells by way of ion channels known as CRAC (calcium-release-activated calcium) currents. Last year, several research groups, including Vigs, identified CRACM1 as being the exact gene that was encoding for this calcium channel.
With the identification of this long-elusive gene, we were able to create a knockout mouse that lacked CRACM1, and [as predicted] these animals proved to be resistant to various stimuli that usually cause severe allergic reactions, she explains. Further experiments demonstrated that mast cells removed from the CRACM1
|Contact: Bonnie Prescott|
Beth Israel Deaconess Medical Center