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CHAPTER 63 IgE production, especially those directed against parasites. In mice, mast cells

BASOPHILS, MAST CELLS, can enhance innate and acquired (IgE-dependent) defense against animal
venoms and also can contribute to host defense in innate immune responses
AND RELATED DISORDERS to certain bacterial infections. Mast cells and basophils also may express pos-
itive and negative immunoregulatory functions through cytokine production
and other mechanisms.
Although a variety of systemic disorders are associated with changes in the
Stephen J. Galli, Dean D. Metcalfe, numbers of blood basophils and many pathologic processes can be associated
Daniel A. Arber, and Ann M. Dvorak* with changes in the numbers of tissue mast cells, patients with primary defi-
ciencies in basophils appear to be exceedingly rare (if they exist at all). Patients
with a primary deficiency of tissue mast cells have not been reported. By con-
trast, neoplastic processes can affect both of the lineages. Increased numbers
SUMMARY of basophils may be present in association with myeloproliferative neoplasms
and several forms of myeloid leukemia. Increased numbers of basophils,
Basophils and mast cells share biochemical and functional characteristics, sometimes to levels of 20 to 90 percent of blood leukocytes, occur in virtu-
but they are not identical. In humans, basophils are the least frequent of the ally all patients with chronic myelogenous leukemia. The basophils associated
three granulocytes, typically accounting for less than 0.5 percent of blood leu- with both chronic myelogenous and acute myeloid leukemias are themselves
kocytes. Basophils circulate as mature cells and can be recruited into tissues, part of the neoplastic clone. The management of patients with “basophilic leu-
particularly at sites of immunologic or inflammatory responses, but they ordi- kemia” can be complicated by shock as a result of massive release of histamine
narily do not reside in tissues. By contrast, mast cells typically are derived from and other mediators in association with acute cytolysis.
blood precursors that lack many of the characteristic features of the mature Disorders of mast cell hyperplasia/neoplasia include solitary mastocy-
cells and complete their maturation in the tissues. The mature mast cells can tomas, the pathogenesis of which is uncertain, the spectrum of disorders
reside in tissues for long periods of time. Mast cells are particularly abundant encompassed in the term mastocytosis, in which significantly increased num-
near blood vessels and nerves and in connective tissues beneath surfaces that bers of mast cells occur in the skin and/or other organs, and mast cell leukemia.
are exposed to the external environment, such as the skin, gastrointestinal The most common form of mastocytosis, indolent systemic mastocytosis,
and urogenital tracts, and respiratory system. Tissue mast cell numbers can typically presents with urticaria pigmentosa involving the skin, although
increase at sites of parasite infection or in association with certain chronic other organs may be involved. Patients with indolent systemic mastocytosis
allergic diseases or other forms of pathology, by recruitment and local matura- have the best prognosis and can expect a normal life span. The prognosis of
tion of blood precursors and by proliferation of resident mast cells. systemic mastocytosis with associated clonal, hematologic non–mast-cell-
Mast cells and basophils express the high-affinity receptor for immuno- lineage disease depends on the course of the associated disease. Patients
globulin (Ig) E (FcεRI) on their surface. Both cell types can be triggered to with aggressive systemic mastocytosis have a guarded prognosis because
release potent mediators in response to activation via FcεRI, for example, when of complications arising from rapid increases in tissue mast cell numbers.
their cell-bound IgE recognizes bivalent or multivalent allergens. Accordingly, Patients with mast cell leukemia, who often present with large numbers of
mast cells and basophils have long been regarded as important effector immature mast cells in the blood at the time of diagnosis, have a fulminant
cells in asthma, hay fever, and other allergic disorders. The cells’ cytoplasmic and rapidly fatal course. Most adult patients with mastocytosis have gain-of-
granule-associated preformed mediators, including histamine and certain function mutations affecting KIT, which encodes the receptor for the major
proteases, their lipid mediators (such as prostaglandin D and leukotriene C ), mast cell growth factor stem cell factor (also known as kit ligand and mast cell
2
4
which are generated upon activation of the cells, and their cytokines, growth growth factor). Some pediatric patients with mastocytosis reportedly have
factors, and chemokines contribute to many of the characteristic signs and the same Asp816Val gain-of-function KIT mutation observed in most adult
symptoms of these diseases. However, several lines of evidence indicate mast patients. Some pediatric patients have a dominant inactivating KIT mutation,
cells and basophils also contribute to protective host responses associated with whereas others lack KIT mutations entirely.

Acronyms and Abbreviations: AML, acute myeloid leukemia; ASM, aggressive cell sarcoma; MMAS, monoclonal mast cell activation syndrome; mMCP, mouse mast
systemic mastocytosis; CML, chronic myelogenous leukemia; CPA3, carboxypep- cell protease; PUVA, psoralen ultraviolet A; qPCR, quantitative polymerase chain
tidase A3; DEXA, dual-energy x-ray absorptiometry; ET-1, endothelin-1; FcεRI, reaction; SCF, stem cell factor; SCT, stem cell transplantation; SM-AHNMD, systemic
high-affinity receptor for IgE; gp120, glycoprotein 120; H&E, hematoxylin and mastocytosis with associated clonal hematologic non–mast-cell-lineage disease;
eosin; HLA, human leukocyte antigen; IFN-α, interferon α; Ig, immunoglobulin; IL, Th, T-helper; TLR, toll-like receptor; TNF-α, tumor necrosis factor α; UP, urticaria
interleukin; ISM, indolent systemic mastocytosis; MCAS, mast cell activation syn- pigmentosa; VEGF, vascular endothelial growth factor; VIP, vasoactive intestinal
drome; MCL, mast cell leukemia; MCP, mast cell–committed progenitor; MCS, mast polypeptide.

* Acknowledgment: This work was in part supported by the Division of Intramural Research, NIAID.

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