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INTRODUCTION

Hematopoietic stem cells that differentiate into common myeloid stem cells give rise to granulocytes that include mast cells (MC), eosinophils, basophils, and neutrophils. In addition to the shared heritage, granulocytes share physical and functional similarities. MCs and eosinophils are popularly known for their presence and function during allergic diseases. Because physicians have noted a clear connection between mast cell activation and the subsequent appearance of eosinophils both within the circulation and in tissues for over a century, MCs and eosinophils are considered together in this chapter.

Both cell types were discovered in the 1870s by the same observer, Paul Ehrlich, who noted that some cells stained in a peculiar fashion when incubated with standard aniline dyes such as toluidine blue and alcian blue. He used the term metachromasie or metachromasia to describe the peculiar color modifications that occurred and the term Mastzellen, meaning “well fed” or “fattened” in German, to describe what we now call MC. Interestingly, this latter term is now known to be a misnomer, since MC cytoplasmic granules are not phagocytized but rather synthesized during cell growth and again during regranulation. Ehrlich also noted that some cells stained intensely when incubated with the acidic dye eosin. As a result, these cells were called eosinophils to mean “eosin lovers.” Both cell types have been evolutionarily conserved (albeit with some differences among species), underscoring their importance to the immune system. Studies of these two cell types, over the ensuing years, have provided great insight into their roles in biology both in health and in disease.

MAST CELLS

The capacity of strategically localized MCs to rapidly release an assortment of powerful chemical mediators makes this cell a unique member of the body’s immune response network. Although most frequently discussed in the context of hypersensitivity immune responses, MCs are also known to participate in normal physiologic processes including gastric acid secretion,1 angiogenesis,2,3 lipid clearance,4–8 and host defense.9,10 MCs also participate in nonallergic pathophysiologic processes such as inflammatory bowel disease,11,12 arthritis,13 scleroderma,14,15 tumors, interstitial pulmonary fibrosis,16–19 envenomation,3,20–23 and atherosclerosis.4,5,24,25 Over the years, basophils have been confused with MC in a number of contexts.26 This confusion is due, in part, to a number of similarities between the cells, including the shared expression of FcεRI (high-affinity receptor for Fc fragment of immunoglobulin E, IgE), release of preformed histamine, and metachromatic staining. However, MCs are mononuclear cells and are almost exclusively localized to tissues. In contrast, basophils are circulating polymorphonuclear cells that are found occasionally in tissue reactions, including the late-phase allergic response. In addition, significant differences in these two cell populations exist in their cell lineage, ultrastructure, mediator release biochemistry, mediator profiles, pharmacology, and surface antigenicity.

Origins of Mast Cells

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