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968 Part VII: Neutrophils, Eosinophils, Basophils, and Mast Cells Chapter 63: Basophils, Mast Cells, and Related Disorders 969

CD63, CD69, and CD203c, and the clinical value of using such find- enhanced ability to express IgE-dependent and/or immunoregula-
ings to monitor basophil activation in vivo (e.g., in the setting of allergic tory functions. 49,74 Exposure of mouse mast cells to certain mono-
disorders or antigen-specific immunotherapy) is under investigation. 65 clonal IgE antibodies, in the absence of exposure to the antigen for
which the IgE is known to have specificity, can enhance the survival
ROLE IN LATE-PHASE REACTIONS of the cells and, in some cases, induce the cells to release all three
74
Mast cells and basophils also can contribute to late-phase reactions. classes of mediators (preformed, lipid, cytokines). Exposure to IgE
in the absence of known antigen also can induce enhanced survival
Late-phase reactions occur when antigen challenge is followed, hours and cytokine and chemokine release in in vitro derived human mast
after initial IgE-dependent mast cell activation, by recurrence of signs cells. Although the mechanisms responsible for these intriguing
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(e.g., cutaneous edema) and symptoms (e.g., bronchoconstriction). 49,50 findings are not fully understood, some types of IgE antibodies
Much of the morbidity associated with chronic allergic conditions, appear to induce aggregation of FcεRI in the absence of known
including allergic asthma, is widely believed to reflect the actions of antigen. 74,76 The clinical implications of these findings, if any,
leukocytes that are recruited to sites of late-phase reactions. 49,50 Stud- remain to be defined.
ies in mast cell–deficient and mast cell knockin mice (genetically mast
cell–deficient mice that have been selectively repaired of their mast cell
deficiency) indicate mast cells are responsible for virtually all of the vas- ROLES IN T-CELL–DEPENDENT RESPONSES
cular permeability changes and leukocyte infiltration associated with
IgE-dependent cutaneous late-phase reactions 66,67 and that TNF-α can, NOT INVOLVING IMMUNOGLOBULIN E
importantly, contribute to these responses. The extent to which mast Mast cell activation and/or infiltration of affected tissues with circulating
66
cells (or TNF-α) contribute to late-phase reactions in humans, in which basophils can occur during a variety of T-cell–dependent immunologic
such reactions may have components that are either IgE or T-cell depen- responses in both humans and experimental animals. 1,5,49,55–57,63,64,77–79
dent (and in which it has been suggested that certain IgE-dependent However, despite years of study, the importance of the contributions of
mechanisms may not involve mast cells ), is not yet clear. 68,69 However, mast cells or basophils in such settings is not fully understood. In part
63
the lymphocytes, basophils, eosinophils, and other leukocytes that are this may reflect differences in the types of mast cell–deficient mice used
recruited to these reactions likely produce cytokines and other medi- to investigate such responses and/or the strain background of such mice,
ators that regulate further development and, ultimately, resolution of and in part this may reflect differences in the details of the experimental
these reactions. 4,5,49,50 models used to probe the roles of mast cells and basophils in these set-
tings (see “Genetic Approaches for Analyzing Basophil and Mast Cell
Function” below). In some of the models of T-cell–dependent responses
ROLE IN CHRONIC CHANGES ASSOCIATED tested, authors have concluded that mast cell can either enhance or
WITH ALLERGIC DISORDERS suppress features of the responses, and in some settings evidence has
been reported that mast cells can enhance the features of relatively weak
Studies in mice (see “Genetic Approaches for Analyzing Basophil responses and suppress features of strong responses. 63,64 It also has been
and Mast Cell Function” below) indicate that mast cells can contrib- proposed that mast cells and basophils might have immunomodulatory
ute importantly to many of the features of asthma, as observed in effects on the development or magnitude of certain acquired immune
certain mouse models of chronic allergic inflammation involving the responses (e.g., positive effects via mast cell–dependent enhancement of
lungs. The features include the development of airway hyperreactivity dendritic cell migration or activation or negative effects via the produc-
to immunologically nonspecific agonists of bronchoconstriction such tion of IL-10 by mast cells). 5,55–57,63,64,78–80 However, some of the findings
as methacholine; infiltration of the airways and lung interstitium with in this area are considered controversial. 5,63,64,79
inflammatory cells, including eosinophils, neutrophils, and T cells;
increased deposition of collagen in the lungs and hyperplasia and/
or hypertrophy of airway smooth muscle; and induction of increased BIOLOGIC FUNCTIONS OF BASOPHILS
numbers of mucus-producing goblet cells in the large airways. 50,70,71
Thus, such mouse models indicate mast cells and their products can AND MAST CELLS
promote the development of much of the pathology and pathophysio- Roles in Host Defense
logic changes observed in longstanding asthma in humans. 50,70,71 Studies Parasites Basophils and mast cells may have critical roles in the
in mice indicate that basophils also can enhance the development of expression of host resistance to certain parasites. Whether basophils,
IgE-dependent chronic inflammation of the skin, even in the absence of mast cells, or both represent major effector cell types in these responses
mast cells or T cells. 56,67 appears to vary according to factors such as species of parasite, species
of host, and site of infection. Thus, in the guinea pig, basophils appear
to be required for expression of immune resistance to infestation of the
IMMUNOGLOBULIN E-DEPENDENT skin by larval ixodid Amblyomma americanum ticks, 77,81 whereas expres-
UPREGULATION OF FcεRI EXPRESSION sion of IgE-dependent immune resistance to the cutaneous infestation
AND FcεRI-DEPENDENT FUNCTION of larval Haemaphysalis longicornis ticks in mice is dependent on mast
57,82
cells and basophils, and IgE.
Such findings support the notion that
As plasma levels of IgE increase (as often occurs in subjects with basophils and mast cells express similar or complementary functions as
allergic diseases or parasite infections), levels of FcεRI expression on effector cells in host defense against parasites and other agents.
the surface of basophils and mast cells also increase. 72,73 Compared Bacterial Infections Studies in mast cell–deficient and “mast cell
with cells with low “baseline” levels of FcεRI expression, such cells knockin mice” (see “Genetic Approaches for Analyzing Basophil and
can bind more IgE, release mediators in response to lower concen- Mast Cell Function” below) or in mice that lack TNF-α or certain mast
trations of allergens, and produce significantly larger amounts of cell–associated proteases indicate that mast cells can contribute to “innate”
74
preformed and lipid mediators and cytokines. Thus, basophils and host defense against some experimental bacterial infections. 63,64,83
mast cells in subjects with high levels of IgE may have significantly Depending on the model system tested, the beneficial role of the mast

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