Regulation of mast cell responses in health and disease

Mast cells are multifunctional cells that initiate not only IgE-dependent allergic diseases but also play a fundamental role in innate and adaptive immune responses to microbial infection. They are also thought to play a role in angiogenesis, tissue remodeling, wound healing, and tumor repression or growth. The broad scope of these physiologic and pathologic roles illustrates the flexible nature of mast cells, which is enabled in part by their phenotypic adaptability to different tissue microenvironments and their ability to generate and release a diverse array of bioactive mediators in response to multiple types of cell-surface and cytosolic receptors. There is increasing evidence from studies in cell cultures that release of these mediators can be selectively modulated depending on the types or groups of receptors activated. The intent of this review is to foster interest in the interplay among mast cell receptors to help understand the underlying mechanisms for each of the immunological and non-immunological functions attributed to mast cells. The second intent of this review is to assess the pathophysiologic roles of mast cells and their products in health and disease. Although mast cells have a sufficient repertoire of bioactive mediators to mount effective innate and adaptive defense mechanisms against invading microorganisms, these same mediators can adversely affect surrounding tissues in the host, resulting in autoimmune disease as well as allergic disorders.