The role of mast cells in disease
Gunnar Pejler, Department of Molecular Biosciences

Mast cells are well known for their harmful effects during allergic reactions such as asthma. However, recent research has implicated mast cells in a variety of other diseases, for example arthritis, multiple sclerosis and cancer. Importantly, all of these diseases are of major human- and veterinary medical concern. Although a role of mast cells in these diseases is becoming established, it is not clear how the mast cells act, i.e. it is not known which of the mast cell gene products that is mainly responsible. When mast cells are activated they release large amounts of a number of potent inflammatory "mediators" from their secretory granule, including histamine, proteoglycans, cytokines and different types of mast cell-specific proteases. Our hypothesis is that the secretion of one or several of these mast cell mediators has important pathological consequences and the aim of this investigation is therefore to systematically study the biological function of each of the mast cell mediators. The approach is to perform targeted deletions of the relevant genes, either genes coding directly for a mast cell mediator or genes coding for enzymes that are involved in the biosynthesis of the respective mast cell mediator. We have recently within the group generated a number of knockout mouse strains, carrying targeted inactivations of various mast cell products. The consequences of the inactivation of the respective gene is studied by both in vivo and in vitro methods. Specific knowledge concerning the function of each of the mast cell mediators may make it possible to intervene with a variety of diseases by specifically targeting the appropriate mast cell mediator.