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CHaPtEr 24 Eosinophils and Eosinophilia 351

from minute to the size of specific granules. Lipid bodies are induced for expression on eosinophils in sites of inflammation.
dissolved by common alcohol-based hematological stains but In addition, eosinophils can express CD40, CD154 (CD40 ligand),
are preserved and stain darkly with osmium fixation. Lipid bodies CD153 (CD30 ligand), CD28 (B7–2), and CD86. 4
lack a delimiting membrane but contain internal membranes Eosinophils express receptors for several lipid media-
that are often obscured by overlying lipid. Lipid bodies are found tors, including PAF and leukotriene B 4 (LTB 4 ), which are
in neutrophils and other cells, especially in association with chemoattractants for eosinophils and stimulate eosinophil
inflammation; but eosinophils typically contain more lipid bodies degranulation and respiratory burst activity. Eosinophils also
compared with neutrophils. Lipid body formation in eosinophils have receptors for prostaglandins D 2 and E 2 and for cysteinyl
is rapidly inducible within minutes. In eosinophils, key enzymes leukotrienes.
involved in eicosanoid formation, including prostaglandin H
synthase, the 5- and 15-lipoxygenases, and leukotriene (LT) C 4 CONSTITUENTS OF EOSINOPHILS
synthase, localize at lipid bodies; and lipid bodies are sites of
eicosanoid synthesis. 7 Eosinophil-specific granules contain preformed proteins that
include both specific cationic proteins and stores of diverse
CELL-SURFACE RECEPTORS AND PROTEINS cytokines and chemokines.
Eosinophil receptors for immunoglobulins include those for Cationic Granule Proteins
immunoglobulin G (IgG), IgE, and IgA. The receptor for IgG Eosinophil granule cationic proteins have been extensively
on eosinophils is principally the low-affinity FcγγRII (CD32), studied because of their abundance in the granules and their
whereas neutrophils have FcγRII and FcγRIII (CD16). capacity to exert multiple effects on host cells and microbial
Eosinophil IgE receptors include the high-affinity IgE receptor targets. Major basic protein (MBP), named for its quantitative
FcεRI, typically found on basophils and mast cells, as well as predominance within the granule and its markedly cationic
FcεRII, the low-affinity IgE receptor, such as CD23, found on (basic) isoelectric point of about 11, is a 13.8- to 14-kilodalton
lymphocytes, monocytes, and antigen-presenting cells (APCs). (kDa) protein. A homolog of MBP that is somewhat smaller
Although FcεRI α-chain protein is present within eosinophils, (13.4 kDa) and less basic (pI 8.7) has been identified. MBP
its surface expression can be low or undetectable. Engagement lacks enzymatic activity and probably exerts its varied effects
of eosinophil FcεRI does not elicit exocytotic degranulation, as via its markedly cationic nature. MBP was found to be toxic to
it does on basophils and mast cells. FcεRI may participate in both airway epithelium and helminths and to have antibacterial
IgE-mediated antigen uptake by antigen-presenting eosinophils. effects. 8
Eosinophil expression of IgE receptors is notable because IgE A second granule protein is eosinophil peroxidase (EPO), an
levels and eosinophil numbers frequently increase concomitantly enzyme distinct from neutrophil myeloperoxidase. Cationic EPO
in helminth infections as well as allergic diseases. (pI 10.8) uses hydrogen peroxide and halide ions to form
Eosinophils express FcαRI (CD89), which binds secretory hypohalous acids, which are toxic for parasites, bacteria, and
IgA more potently than other forms of IgA. Engagement of FcαRI tumor and host cells. EPO utilizes bromide in preference to
triggers eosinophil release of granule proteins. With the char- chloride and is even more active with a pseudohalide, thiocyanate,
acteristic localization of eosinophils to mucosal surfaces of the to generate oxidant products, including hypobromous and
respiratory, GI, and genitourinary tracts, this IgA receptor enables hypothiocyanous acids.
eosinophils to engage secretory IgA present at these mucosal Two additional granule proteins are eosinophil cationic protein
sites. (ECP) (18 kDa, pI 10.8) and eosinophil-derived neurotoxin
Eosinophils have receptors for complement components, (EDN) (18–19 kDa, pI 8.9). EDN, never demonstrated to be
including C1q (CR1), C3b/C4b (CR1), iC3b (CR3), C3a, and neurotoxic for humans, is so named only because, after it is
C5a. Both C3a and C5a are eosinophil chemoattractants and injected intracerebrally into test rabbits, it elicits a characteristic
stimulate the production of oxygen radicals by eosinophils. neuropathological response. Both ECP and EDN are ribonucleases
Eosinophils express several receptors for chemokines. CCR1 is (RNases). EDN expresses 100 times more RNase activity compared
a receptor for MIP-1α, MCP-3, and RANTES, whereas CCR3 is with ECP, although their toxic effects on bacterial, parasitic, and
a receptor for eotaxin-1, eotaxin-2, eotaxin-3, MCP-3, and mammalian target cells are not simply a result of their RNase
RANTES. Eosinophils express CXCR4 and respond to the ligand catalytic activities.
for this receptor, stromal cell–derived factor 1α. Within the specific granule, MBP is localized to the crystalloid
Mature eosinophils, like their immature precursors, express core and to tubulovesicular structures within and arising from
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receptors for the three cytokines, GM-CSF, IL-3, and IL-5, which the granules, whereas ECP, EDN, and EPO are localized in the
promote eosinophilopoiesis and stimulate the functioning of matrix of the granule around the core (see Fig. 24.2). MBP is
mature eosinophils. In addition, eosinophils have receptors for also found in low amounts (~3% of eosinophil levels) in basophils,
a broad range of other cytokines, including IL-1α, IL-2, IL-4, but whether this reflects endocytosis or endogenous synthesis
interferon (IFN)-α and IFN-γ, tumor necrosis factor (TNF)-α, is not known. Uptake of MBP and EPO into mast cells is known
stem cell factor (c-KIT), and IL-16 (which signals via CD4 on to occur via endocytosis. Small amounts of EDN and ECP are
eosinophils). Thus eosinophils are subject to stimulation by many present in neutrophils, and as neutrophils contain messenger
cytokines, although little is understood about how many of them RNA (mRNA) transcripts for these, EDN and ECP are likely
affect eosinophil functioning in vivo. synthesized by neutrophils. Nevertheless, eosinophils are the
Of pertinence to interactions between eosinophils and B and dominant source of these four cationic proteins. The properties
T lymphocytes, eosinophils can express several relevant plasma of these proteins and their numerous biological effects have been
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membrane proteins. Class II major histocompatibility complex reviewed, as these proteins have major effects not only in the
(MHC) proteins, generally absent on blood eosinophils, are potential role of eosinophils in host defense against helminth