Asthma is a chronic condition that adversely impacts the airway passages. This disease presents as episodic events typified by difficulty in breathing as a result of obstruction of the airways as well as inflammatory responses. This condition is provoked by response of the immune system to allergens. The inflammatory response manifests itself by the enhanced production of interleukin-4 (IL-4), increased activity of a particular subset of T helper lymphocytes (TH2) and serum immunoglobulins. A link has also been established between proteinases – enzymes that cleave proteins, the immune Toll-like receptor 4 (TLR4) and asthma. These proteinases that have been shown to initiate TH2-mediated allergic reactions are secreted by fungi, pollen and dust mite antigens.
A full understanding of the underlying factors that trigger asthmatic episodes would, of course, be invaluable in developing therapeutic strategies to treat this illness. Dr. Valentine Ongeri Millien and colleagues from the Translational and Molecular Medicine Program at Baylor College of Medicine at Houston Texas have made some important discoveries in this light. The research efforts of this investigative team have established that airway- derived proteinases trigger allergic disease and innate immunity against fungal infection. Furthermore, they have shown that these particular outcomes were a direct result of the breakdown of fibrinogen, an essential clotting factor, by these proteinases. It is the products of this breakdown that bind to TLR4 on both epithelial cells that line the airways and to macrophages – a type of circulating cell of the immune system that has the role of ingesting invading infectious agents. From these results, it seems apparent that inflammation of the airways that is characteristic of asthma is a direct result of the immune antifungal defense strategy.
The Elucidation of this mechanism may prove to be invaluable in terms of developing therapeutic strategies for the treatment of allergen-induced pulmonary diseases such as asthma. In fact, this group when on to show that the use of hirudin, a drug that functions as a potent protease inhibitor, can lessen the severity of allergic lung disease. This may prove to be a very important finding.