A team of Penn State University researchers is the first to demonstrate that lipid molecules in cell membranes participate in mammals' reactions to allergens in a living cell.
The finding will help scientists better understand how allergy symptoms are triggered, and could contribute to the creation of improved drugs to treat them. The work will be reported in the 14 March issue of the Journal of Biological Chemistry.
The team studied clusters of cholesterol-rich lipid molecules that they believe serve as platforms for the receptors that receive antibodies, the proteins that protect the body from allergens. In this case, the team examined IgE antibodies, which upon binding to their receptors initiate a cell's release of histamine--the substance that causes the unpleasant, but beneficial, mucous production, congestion, and itchiness associated with allergies. "This research is basically the molecular foundation for why many people sneeze in the spring," said Ahmed Heikal, an associate professor in the Department of Bioengineering and a leader of the project.
While the idea that lipid clusters--also known as lipid domains--are involved in the allergic response is not new, the Penn State team is the first to document this connection in a living cell under physiological conditions. "No one has observed the domains in action because they are too small and too transient--held together by very weak molecular interactions--to be viewed with a light microscope," said Erin Sheets, a Penn State assistant professor of chemistry who also is a leader of the project. "To overcome this challenge," added Heikal, "we used a combination of imaging and spectroscopy techniques that we are developing in our laboratories.
In their experiment, the researchers first labeled the cell membrane and IgE antibodies with two different fluorescent tags. Next, they introduced an allergen and watched as it bound to receptors on the cell membrane, thus initiating an allergic response.