Scientists have found something that the drugs against asthma and allergies can be improved. To a higher level The TLR4 receptor, present on epithelial and immune cells, are indispensable in the molecular chain reaction that causes an allergic reaction.
Asthma and allergy
Asthma and allergy are sometimes called diseases of the 21st century. It is because to a large extent they have made a strong advance in the Western world during the last decades and because of the typical lifestyle diseases. Currently, between 15 and 20 percent of the Belgian and Dutch population regularly have complains of an allergic reaction. Most worrying thing is the situation in children: less than 30 percent have some allergy and 10 percent of them are chronic asthma sufferer. Scientists did all research for years in the microbiological background of allergic reactions. The main question is: why we see in with one patient an overreaction of the immune system with allergy or asthma, and the other not? This research focuses not so much on the allergens, the harmless substances against which the body performs an unnecessary battle. They are well known: dust mites on pollen and bee venom. Where researchers have been looking for in this field, is that why the immune system, without any good reason for it, overreacts.
Scanning cells (dendritic cells)
Our immune system recognizes and evaluates the external substances that enter our body by using a special type of immune cells; called dendritic cells (abbreviated DC’s). The DC’s scan our bodies constantly and detects the presence of foreign substances and pathogens. Therefore they are located in places where allergens usually enter the body, such as in the skin and in the mucous membranes of the respiratory tract.
So why the DC’s are not just turned off? ”Patients would indeed not have asthma or allergies more, but they would suddenly become very susceptible to viral infections,” says Bart Lambrecht, world authority in asthma research and director of the Department for Molecular Biomedical Research at the Flanders Institute for Biotechnology ( VIB ). “In other words, the therapy should not be worse than the disease. That is the core of the problem. Every action of our immune system is controlled by the DC’s. DC’s central control of our immune system”. When Lambrecht was still working at the UZ Gent, as a clinical researcher, he succeeded with his colleagues in some interesting breakthroughs in activation of DC to identify between virus, cancer, and allergen recognition. He discovered that a key protein receptor – called TLR4- selectively inhibits the allergic response. Lambrecht’s group then succeeded to neutralize the TLR4 (in the line of the lungs and airways) through medication receptor on epithelial cells causing the DC were activated in a slower pace after entry of allergens. Experimental animals were found to have less suffering from asthma but they were not entirely free asthma.
Mice without allergy
There is a good explanation for it, because theTLR4 receptor is not only stimulated by allergens with reference to a study published this week in the journal Science. American researchers at Baylor College of Medicine (Houston, Texas) have found that TLR4 is also stimulated by a substance in the body. It is stimulated especially by degradation of fibrinogen also known as coagulation factor 1. The researchers genetically engineered mice in which the fibrinogen was not degraded in the blood and then mice were exposed to different allergens. What was found: the mice showed no allergic reaction even if they were inhaled spores of fungi Scientists think their studies revealed the crucial and indispensable part of the chain reaction that causes an allergic reaction. Indeed, it is likely that the molecular chain reaction that results in an allergic reaction make a detour along the blood clotting protein fibrinogen (more specifically its degradation products). The Americans even think that the allergic reaction can’t start before the TLR4 receptor is activated by degradation of fibrinogen. TLR4 is a new therapeutic target that a new generation can bring medicines for allergy and asthma. Bart Lambrecht, who already had a suspicion that TLR4 is not only stimulated by allergens, also finds it as an important discovery in the allergy research. What Lambrecht and his colleagues discovered in 2009 was that products that interfere with blood clotting; such as some medicines can affect asthma has an Inhibitory influence.