Cell structure biochemistry and activation

The nucleus of the mature eosinophil is segmented, with an average lobe index of approximately 2.1. The cytoplasm of the eosinophil is filled abundantly with secretory granules. The large granules have a central crystalloid body and a surrounding matrix containing cationic proteins that are responsible for the binding of acidic dyes, such as eosin. Small granules can also be observed by electron microscopy. These have many of the same constituent substances as the large granules and may represent a precursor or remnant of the large granule rather than a separate class of granule.

The cytoplasm also contains lipid bodies, glycogen and prominent Golgi bodies, and large amounts of lysophospholipase. This enzyme can form crystals of a characteristic shape (bipyramidal needle), known as Charcot-Leyden crystals, which are occasionally found within the eosinophil and more commonly at the site of inflammation in tissues (Figure 1).

The eosinophil surface membrane displays receptors for immunologically active substances, including

Figure 1 Transmission electron micrograph of normal human blood eosinophil. The characteristic features include a segmented nucleus (N), secretory granules with an electron-dense crystalloid core (arrowheads), a lipid globule (L) and a prominent Golgi apparatus (GA). Magnification x 20 000. (The figure was kindly provided by Dr Khwaja Siddiqui.)

Figure 1 Transmission electron micrograph of normal human blood eosinophil. The characteristic features include a segmented nucleus (N), secretory granules with an electron-dense crystalloid core (arrowheads), a lipid globule (L) and a prominent Golgi apparatus (GA). Magnification x 20 000. (The figure was kindly provided by Dr Khwaja Siddiqui.)

C3a/C5a, C3b, iC3b, Fct (FcyRII), Fee (FceRII), Fca, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (1L-3), IL-5, tumor necrosis factor (TNF), and other cytokines, the chemokines RANTES, MlP-la, MIP-lfJ, MCP-3 and eotaxin, mast cell-derived ECF-A tetrapeptides, and formyl-methionyl peptides. Other surface structures involved in immunologic functions include CD4, IL-2R (gp55), LFA-1 and 3, VEA-4 and HLA-DR antigens.

Stimulation of eosinophils through Fc or complement surface membrane receptors induces the directional release of secretory granule contents, the activation of a respiratory burst and associated release of oxygen metabolites, and the release of pharmacologically active lipid metabolites (Table 1).

Eosinophil secretory granules have a crystalline core composed of major basic protein (MBP), an 11 kDa cationic protein that is toxic to a variety of tissues and microorganisms. The matrix surrounding the core contains the structurally related eosinophil cationic protein (ECP, 18-22 kDa), eosinophil-derived neurotoxin (EDN, 18-19 kDa), the eosinophil peroxidase (EPO), elastase, coltagenase, arylsulfatase B, |3-glucuronidase, histaminase, phosphatases, phospholipase B and D, catalase, nonspecific esterases, and proteoglycans. The EPO is

Table 1 Functions of activated eosinophils

• Phagocytosis of immune complexes and certain microorganisms (e.g. Escherichia coii, Candida albicans, Trypanosoma cruzi)

• Directional release of secretory granule substances, including the toxic cationic proteins MBP, ECP, EDN, lysosomal enzymes and EPO

• Release of toxic oxygen metabolites including 02 and H202. In the presence of the peroxidase and halide ions, H202 is converted to hypohalous acid, preferentially HOBr

• Release of pharmacologically active lipid metabolites, including minor amounts of leukotriene B4, major amounts of leukotriene C4 and D4, 15-HETE

(15-hydroxyeicosatetraenoic acid), platelet activating factor, prostaglandins E,, E2 and thromboxane Bz

• Release of cytokines, including IL-1, IL-2, IL-5, IL-6, IL-8, TNF and TGFa structurally different from the neutrophil myeloperoxidase and is relatively insensitive to cyanide.

The respiratory burst is associated with increased uptake of glucose and oxygen, hexose monophosphate shunt activity, the oxidation of NADPH, and the reduction of 02 to 02. 02, in the presence of superoxide dismutase, is converted to H202, which is converted to hypohalous acid, preferentially HOBr, in the presence of EPO and halide ions.

Activated eosinophils are important sources of the lipid metabolites leukotrienes C4 and D4 (slow reacting substance of anaphylaxis) and platelet activating factor, with a release of 100 ng 10 6 cells or more of each mediator measured in some experiments, quantities substantially greater than those released by mast cells.

Eosinophils are also important sources of multiple cytokine species, including IL-5, which can provide positive feedback on eosinophil development, and transforming growth factor a (TGFa), which promotes tumor angiogenesis.

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