European Respiratory Journal 2019; DOI: 10.1183/13993003.00685-2019
It is now well established that mast cells play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on mast cell-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which mast cells influence asthma pathology. Mast cells contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of mast cell-restricted proteases. When mast cells are activated, e.g.in response to IgE receptor crosslinking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The mast cell-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly though, the role of the mast cell-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, I review the current knowledge of how the mast cell-restricted proteases impact on asthma.
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Conflict of interest: Dr. Pejler has nothing to disclose.