VCU news

By Sathya Achia Abraham

Severe allergic reactions are rare, but when they occur it takes just seconds for life-threatening anaphylactic shock to set in, requiring immediate emergency treatment. Some triggers include insect toxins, shellfish, peanuts, tree nuts, cow’s milk, eggs, latex and medications — most commonly penicillin.

Anaphylaxis is a rapidly developing and serious allergic reaction that affects a number of different areas of the body at one time. This collection of rapid changes to the skin, blood vessel and lung systems is the least understood among allergic disorders. However, researchers are looking for ways to better understand what takes place in anaphylaxis to best prevent this dangerous allergic reaction.

Virginia Commonwealth University School of Medicine researchers, led by Carole A. Oskeritzian, Ph.D., assistant professor in the Department of Biochemistry and Molecular Biology, have been examining the roles of sphingosine-1-phosphate, or S1P, and its S1P₂ receptor in developing and mature human mast, and also in a mouse model of anaphylaxis.

Mast cells react to allergy-causing agents by releasing substances that trigger the body’s allergic response, leading to conditions like asthma and hives. Among the molecules released by mast cells that participate in the allergic response is S1P.

In a study published online this week in the March issue of the Journal of Experimental Medicine, the VCU team reported that S1P and its S1P₂ receptor activate mast cells and thereby are able to contribute to severe allergic reactions. They further observed that blocking S1P access to S1P₂ dramatically decreased the ability of human mast cells to become hyperactive.

“We discovered that antagonizing S1P₂ with a pharmacological compound, or S1P₂ deficiency in mice, both resulted in decreased severity of the signs associated with anaphylaxis, including blood levels of mast cell-derived mediators and edema around the blood vessels in the lungs,” explained Oskeritzian.

According to Oskeritzian, specifically targeting the S1P₂ receptor may have important clinical and therapeutic implications for allergic diseases.

“Activation of mast cell S1P₂ may be critical in determining the extent of anaphylactic shock, and could be a novel therapeutic strategy to control not only acute life threatening exacerbations of anaphylactic shock, but also other inflammatory diseases where mast cell activation has been identified as critical trigger and promoter, such as rheumatoid arthritis and atherosclerosis,” she said. 

“Because there is no cure for allergies, we need to think about new targets, new ideas and new strategies to help design a cure, prevent them and keep them under control, and interfering with the interaction of S1P with its S1P₂ receptor might be a way to achieve this goal,” Oskeritzian said.

This work was supported by grants from the National Institutes of Health.