RSS Feeds

Email a Friend Printer Friendly

Blocked gene may provide new treatment for allergies

December 05, 2001

Allergic reactions like hay fever can recur over long periods since the allergenic mast cells survive and revive.  A team of Uppsala scientists have now identified the mast cell's survival gene, and by blocking this gene, they can inhibit allergic reactions, opening new avenues for treatment.  These findings have been published in Monday's issue of The Journal of Experimental Medicine. 
It has long been known that long-lived mast cells are a precondition for allergic reactions, in hay fever, for example.  People who run a high risk of being affected by allergies can have extremely high mast-cell counts.  To generalize it could even be said: "No mast cells, no allergy."  When an allergy-producing substance, an allergen, such as pollen, enters the body of a person with an allergy, it is bound up by IgE-antibodies located on the surface of the mast cell.  When IgE, that is, immunoglobulin E, binds the allergen, the mast cell is activated, releasing various substances, such as histamine, that cause allergic symptoms like a runny nose, swelling, and itching.  The allergenic mast cell survives allergic activation and can later be reactivated.  This means that the allergic reaction can persist and people can suffer from their allergy over and over again during the pollen season, for instance.
Most inflammatory cells die after they have been activated, but the allergenic mast cell survives its activation.  A team of researchers at Uppsala University in Sweden, Zou Xiang, Ahmed Ahmed, Christine Möller, and Gunnar Nilsson, can now demonstrate that this ability is due to a gene, A1, that keeps the mast cell from committing suicide, so-called programmed cell death.  When mast cells are activated by IgE, the amount of A1 increases, but when A1 is blocked, the mast cell does not survive an allergic reaction.  Experiments on mice that lack the A1 gene show that mice have fewer mast cells after having been exposed to an allergic reaction.  The project is being carried out in collaboration with Innoventus Uppsala Life Science.
The discovery that the A1 gene is important to the survival of mast cells in connection with allergies can mean that there can be a new 'target' for developing new drugs for allergies.  Today's allergy medicines inhibit the effect of what the mast cells release, for instance histamine.  By blocking the effect of A1, these scientists hope it will be possible to come up with methods for treating allergies that directly target the allergenic mast cell.  Since the A1 gene seems to be play a role only after the mast cell has been activated by an allergenic substance, the only cells that would be blocked would be those participating in an allergic reaction.  Instead of surviving activation, the mast cell would die as a result of the blocked A1, which in turn would lead to fewer mast cells and milder allergic symptoms.
The new findings are presented in the latest issue of The Journal of Experimental Medicine, December 3, 2001.  The title of the article is "Essential role of the prosurvival bcl-2 homologue A1 in mast cell survival after allergic activation." Authors: Z. Xiang, A.A. Ahmed, C. Möller, K.I. Nakayama, S. Hatakeyama, and G. Nilsson.

Vetenskapsrådet (The Swedish Research Council)