IntroductionMast cells have a rather unique position among cells of the immune response. Their progenitors are bone marrow derived, yet under normal conditions appear in the mature state only within vascularized tissues, where they are long-lived. Mast cells appear historically ancient, 1 yet their roles in mammalian biology, including disease pathogeneses and host defense mechanisms, often remain speculative and based on in vitro studies and animal models 2-4 with 2 primary exceptions-IgE-mediated immediate hypersensitivity reactions and mastocytosis. Complicating the understanding of the role of mast cells in human biology is that while other normal human immune cell functions often become more obvious in the absence of a specific cell type, such as with agranulocytosis, or in the absence of normal function of a specific pathway, as in autoimmune lymphoproliferative syndrome (ALPS) associated with defective lymphocyte Fas-mediated apoptosis, the single similar situation involving mast cells and human disease characterized to date is mastocytosis, resulting from disturbed control of mast cell proliferation.Mast cell research initially relied upon observation on mast cell appearance and numbers in tissue biopsies, sometimes correlated with tissue histamine levels. With time, methods were developed to obtain and study mast cells ex vivo. The most common protocols relied on obtaining mast cells from the peritoneal cavity of rodents, or enrichment of mast cells from tissue digests. These approaches initiated modern mast cell biology with the first work on histamine, slow-reacting substance of anaphylaxis (SRS-A), and other mast cell-derived mediators including proteases, and the early studies on the mechanisms of mast cell signal transduction. In more recent years, and with the identification of key mast cell growth factors, investigators have discovered how to culture mast cells in vitro from pluripotential precursors (Figure 1). This development has facilitated the further study of human mast cell gene expression, signal transduction, and production of mediators relevant to inflammation.
HistoryThe most striking feature of mast cells is that their cytoplasm is filled with dense metachromatic granules that stain red or violet when treated with basic aniline dyes. Using this "metachromasia," Ehrlich in 1878 first clearly described mast cells or "mastzellen" (maestung-a root of the English word mastication; the active form "measten" is still in use). 5 He speculated that these granules were the product of overfeeding (die mast). Ehrlich also noted the tendency of mast cells to be associated with blood vessels, nerves, and glandular ducts. These observations contributed to Ehrlich's Nobel Prize in Medicine in 1908. In 1894, Unna reported that the cutaneous lesions termed urticaria pigmentosa (UP) were associated with increased mast cells below each lesion. 6 Thus, by the end of the 19th century, mast cells had been recognized both in the normal state and associated with pathology.Following a number of reports that ma...