New millennium: The conquest of allergyThe diverse potential effector and immunoregulatory roles of mast cells in allergic disease☆,☆☆,★
Section snippets
Mast cell development, distribution, and heterogeneity
Mast cells are derived from CD34+ hematopoietic progenitor cells and, except for the small numbers of mast cells that reside in the bone marrow, maturation typically occurs in the peripheral tissues.1, 2, 3, 4, 5 Several lines of evidence indicate that interactions between the tyrosine kinase receptor c-kit, which is expressed on the surface of mast cells and their precursors, and the c-kit ligand, stem cell factor (SCF), are essential for mast cell development and survival both in mice and
“Mast cell knock-in mice”: A model for analyzing mast cell development and function in vivo
IgE-associated immune responses and other inflammatory processes typically involve the coordinated and potentially redundant activities of several cell types; under these circumstances, characterizing the specific contributions of a single cell can be difficult. In the case of the mast cell, this problem can be addressed by use of genetically mast cell–deficient KitW/KitW-v mice.1, 14, 16 These mice are anemic and virtually lack tissue mast cells, germ cells, melanocytes, and interstitial cells
Mast cell mediators
Mast cells contain, or elaborate on appropriate stimulation, a diverse array of potent biologically active mediators that can have many different potential effects in inflammation, tissue remodeling, and organ function at sites of mast cell activation (Fig 2).4, 5, 6, 7, 8, 15, 23, 24, 25, 26, 27, 28, 29
Mast cells and IgE-associated immune responses
It is useful to think of the effector phases of IgE-associated immune responses as occurring in 3 temporal patterns: (1) acute reactions, which develop within seconds or minutes of allergen exposure, (2) late-phase reactions, which develop within hours of allergen exposure, often after at least some of the effects of the acute reaction have partially diminished, and (3) chronic allergic inflammation, which can persist for days to years.
Conclusions
Data derived from “mast cell knock-in mice” support the notion that mast cells not only represent the key effector cells of acute IgE-dependent reactions but also can contribute significantly to certain features of IgE-associated late-phase reactions and chronic allergic inflammation (Table I).
Mast cells are derived from hematopoietic precursors but typically complete their maturation and reside in peripheral connective tissues (by contrast, basophils generally
Acknowledgements
Dr Galli has consulted for Genentech, Inc, under terms that are in accord with Stanford University conflict-of-interest guidelines.
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Series editors: Donald Y.M. Leung, MD, PHD, Stanley J. Szefler, MD, and Harold S. Nelson, MD
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Supported by a grant from Novartis Pharmaceutical Corp., East Hanover, NJ
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Reprint requests: Stephen J. Galli, MD, Department of Pathology, L-235, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305-5324.