Jump to content
Powered by

Mast cells as the central and pivotal points of allergy processes

Mast cells of the human immune system play a key role in allergic and inflammatory reactions. Activated mast cells release a number of substances that mediate an immune response. The process by which such mediators are released is still largely unknown. Scientists from the University of Hohenheim are focusing on finding out how allergic reactions are induced by mast cells.

Mast cells play an important part in allergic reactions (here: IgE-mediated type I reaction) © Lorentz, University of Hohenheim
Mast cells are present in all tissue boundaries between the outside world and the internal milieu. Examples of such boundaries include the skin and the mucosa of the digestive tract. Allergic reactions are boosted by activated mast cells. Before the mast cells bind to allergens, other immune system cells will already have recognised normally harmless substances as highly dangerous and produced IgE antibodies that bind to the allergens. The subsequent activation of mast cells can have far-reaching consequences: The binding of an allergen to IgE triggers a signalling cascade in the mast cells, which leads to the release of stored (granules) or newly synthesised substances. These substances mediate an immune response which leads to allergy symptoms. “Over the last few years, it has been shown that mast cells not only release pro-inflammatory substances, but also growth factors, cytokines and chemokines,” said Dr. Axel Lorentz from the University of Hohenheim who is investigating the effect of mediators that are released by mast cells. He hopes that his work will provide him with insights into how the release of mediators and the onset of allergic reactions can be prevented. The release of mediators is a highly complex and highly regulated process. The mediators are packaged into membrane-coated vesicles which then migrate towards the cell membrane where they interact with proteins that trigger the fusion of the vesicle membrane with the cell membrane. Proteins that have similar functions in nerve cells have previously been detected and classified. These proteins are referred to as SNAREs (soluble N-ethyl-maleimide-sensitive factor attachment protein receptors). The SNAREs mediate the exocytosis of the cellular transport vesicles with the cell membrane, a process which leads to the release of mediators.

Mediators are released by way of exocytosis

Mast cells are isolated from human intestinal mucosas and purified. © Lorentz, University of Hohenheim
SNARE molecules that are located in the membrane of the transport vesicles are referred to as v-SNAREs; molecules in the cell membrane are known as t-SNAREs. “t” stands for “target” (i.e. target membrane), which in this case is the cell membrane. Effective exocytosis depends on the cooperation between the t- and v-SNARE proteins. The SNARE complex is a helix bundle of protein chains. “The membranes contain enzymes that catalyse the formation of helices, which brings the membranes into close vicinity to each other. This is where exocytosis starts,” said Lorentz. There are numerous SNARE protein isoforms, which makes the clarification of their function rather time-consuming. In order to collect as much material as possible for his investigations, Lorentz works with hospitals that provide him with parts of human intestines with the patients’ agreement. “We depend on this cooperation with hospitals to obtain the necessary material. When colon cancer patients undergo surgery to have a diseased section of their intestine removed, the tumour specimen that has been removed usually contains some healthy tissue which we can use for our work,” said Lorentz.

SNARE proteins are potential therapeutic targets

Mast cell degranulation by way of exocytosis depends on the fusion of vesicle membrane and cell membrane. © Lorentz, University of Hohenheim
Lorentz then isolates the mast cells to look for combinations of SNARE proteins that act together in order to induce exocytosis. “We have already characterised some SNARE proteins that form SNARE complexes in human mast cells. We have also been able to show that no mediators are released when protein function is switched off,” said Lorentz explaining that his team had to find a method to inhibit or destroy the proteins. “A smart method was already being used for work with neurotoxins; however, this only worked for neuronal SNAREs,” said Lorentz who is now using specific antibodies that bind to the N terminus of SNARE proteins, which are then no longer able to bind to their counterpart, thereby preventing the fusion of the membranes. In addition to SNAREs, there are a number of adapter molecules that complicate the matter further. These molecules have different functions, which are not yet known in detail. At present, it is not possible to say whether these molecules could be used as therapeutic targets.” Although we focus mainly on basic research, we are also always looking for targets that would enable us to develop suitable allergy treatments,” said Lorentz.

Further information:
University of  Hohenheim
Institute of Food Science
PD Dr. Axel Lorentz
Fruwirthstr. 12
70599 Stuttgart
Tel.: +49 (0)711 459-24391
E-mail: lorentz(at)uni-hohenheim.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/mast-cells-as-the-central-and-pivotal-points-of-allergy-processes