Calcium Channels Crucial In Asthma Onset

Researchers at Beth Israel Deaconess Medical Center (BIDMC) have found that calcium channels have a crucial role to play in the onset of asthma and other allergic reactions.

They also explained that calcium ion channels called ‘calcium-release-activated calcium’ (CRAC) currents, play a pivotal role in activating mast cells.

The study was led by Monika Vig, PhD, an investigator in the Department of Pathology at BIDMC and Instructor of Medicine at Harvard Medical School, who said that earlier mast cells were the only factor, that were known for their role in allergic reactions.

“Mast cells store inflammatory cytokines and compounds [including histamine and heparin] in sacs called granules. When the mast cells encounter an allergen – pollen, for example – they ‘degranuate,’ releasing their contents and triggering allergic reactions,” Nature immunology quoted her, as explaining.

But now, mast cells are also known to play a key role in a number of biological processes and are involved in diseases ranging from multiple sclerosis and rheumatoid arthritis to cancer and atherosclerosis. To function, they require a biological signal, specifically, calcium.

Calcium moves in and out of the cells by way of CRAC currents. In fact, Last year, many researchers identified that CRACM1 gene 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 explained.

Later the experiments revealed that mast cells removed from the CRACM1 knockouts were not able to take in calcium, and thus they could not trigger allergic responses when exposed to allergens.

“These findings provide the genetic demonstration that CRAC channels are essential in mast-cell activation. This provides the proof of concept that an inhibitor of the CRAC channel should be able to impact mast-cell related diseases, including asthma and allergic diseases,” notes senior author Jean-Pierre Kinet, MD, BIDMC Professor of Pathology at Harvard Medical School.

“Since mast cells are also known to contribute to the progression of several other debilitating diseases, including multiple sclerosis, rheumatoid arthritis and cancer, an inhibitor of the CRAC channel could, in the future, help in slowing the progression of these diseases as well as alleviate disease symptoms,” she added.

The findings of this study appeared in the recent issue of Nature Immunology

Source-ANI
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