New millennium: The conquest of allergy
The diverse potential effector and immunoregulatory roles of mast cells in allergic disease,☆☆,

https://doi.org/10.1067/mai.2000.106485Get rights and content

Abstract

Mast cells are of hematopoietic origin but typically complete their maturation in peripheral connective tissues, especially those near epithelial surfaces. Mast cells express receptors that bind IgE antibodies with high affinity (FcϵRI), and aggregation of these FcϵRI by the reaction of cell-bound IgE with specific antigens induces mast cells to secrete a broad spectrum of biologically active preformed or lipid mediators, as well as many cytokines. Mast cells are widely thought to be essential for the expression of acute allergic reactions, but the importance of mast cells in late-phase reactions and chronic allergic inflammation has remained controversial. Although it is clear that many cell types may be involved in the expression of late-phase reactions and chronic allergic inflammation, studies in genetically mast cell–deficient and congenic normal mice indicate that mast cells may be critical for the full expression of certain features of late-phase reactions and may also contribute importantly to clinically relevant aspects of chronic allergic inflammation. Moreover, the pattern of cytokines that can be produced by mast cell populations, and the enhancement of such cytokine production in mast cells that have undergone IgE-dependent up-regulation of their surface expression of FcϵRI, suggests that mast cells may contribute to allergic diseases (and host defense) by acting as immunoregulatory cells, as well as by providing effector cell function. (J Allergy Clin Immunol 2000;105:847-59.)

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

. Diagrammatic representation of some of the major mediators, cytokines, and growth factors that are produced on IgE- and antigen-dependent activation of mast cells and the potential

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).

. Key concepts of mast cell biology

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

    ☆☆

    Supported by a grant from Novartis Pharmaceutical Corp., East Hanover, NJ

    Reprint requests: Stephen J. Galli, MD, Department of Pathology, L-235, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305-5324.

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