Inflammatory cells in asthma: Several types of inflammatory cells comprise the distinctive infiltrate seen in this disease. Some features of eosinophils, mast cells, and basophils are discussed below.

Eosinophils

Circulating eosinophil and neutrophil: A Wright-stained blood smear shows an eosinophil with a bilobed nucleus and red specific granules (left panel) and a neutrophil (right panel).

Ultrastructure of eosinophil: This electron micrograph shows 3 portions of the bilobed nucleus (N), a primary granule (arrow), and multiple specific granules (* marks one) that stain red with the H&E stain. Primary granules contain Charcot-Leyden crystal (CLC) protein [1]. The specific granules have a dark crystalloid core and a paler matrix. The dark core contains major basic protein, and the matrix contains eosinophil peroxidase, neurotoxin, and cationic protein [2].

Higher magnification of eosinophil

Eosinophils develop from CD34+ bone marrow precursors. They circulate in the blood and reside at mucosal surfaces in tissues. IL-5, which promotes differentiation, maturation, and activation, also causes their degranulation. Granule proteins are transferred to the exterior directly, by fusion with the plasma membrane, or indirectly, via small vacuoles. Matrix and core proteins can be emptied separately (by piecemeal degranulation) or together. With degranulation, CLC protein becomes localized diffusely in the cytoplasm and nucleus [3].

The electron micrographs were provided by Dr. Dorothy Bainton.

Functions of the eosinophil in asthma: Inflammation usually has some beneficial effect for the host (e.g., eradication of infection), but eosinophils in asthma appear to be mainly harmful. Release of granule proteins is associated with denudation of respiratory epithelium, airway hyperreactivity, and edema. Eosinophil-derived platelet activating factor and leukotriene C4 may be associated with bronchoconstriction [2,4].

Charcot-Leyden crystals are a frequent finding in any type of inflammatory infiltrate with large numbers of eosinophils. In asthma, the crystals are usually found extracellularly in mucous plugs. They have the shape of two hexagonal pyramids joined at their bases and can measure up to 50 µm in length. Crystals, 2-3 µm in size, have been found in macrophages in the vicinity of conglomerates of eosinophils. Macrophage uptake may represent a disposal system [1]. Noncrystalline CLC protein is found in the primary granules of eosinophils. When the cell becomes activated or damaged, CLC protein reactivity is found scattered diffusely over organelles of the cytoplasm and nucleus. In addition, CLC protein is located as crystals in primary granules of basophils. After basophil degranulation, the protein is found diffusely in the cytoplasm and nucleus, but it is not released extracellularly [5,6]. The CLC protein has lysophospholipase activity. One hypothesis concerning its function is that the lysophospholipase inactivates cell-damaging lysophosphatides produced during membrane metabolism during degranulation [6].

Charcot-Leyden crystals: The cells in the photo are a mass of eosinophils in a patient with an IL-5 producing lymphoma. Multiple large, extracellular Charcot-Leyden crystals that show a bipyramidal shape (upper right) and hexagonal cross-section (lower left) are present.

References

1. Dvorak A, Weller P, Monahan-Earley R, Letourneau L, Ackerman S. Ultrastructural localization of Charcot-Leyden crystal protein (lysophopholipase) and peroxidase in macrophages, eosinophils, and extracellular matrix of the skin in the hypereosinophilic syndrome. Lab Invest 1990; 62:590-607.

2. Gleich G, Flavahan N, Fujisawa T, Vanhoutte P. The eosinophil as a mediator of damage to respiratory epithelium: a model for bronchial hyperreactivity. J Allergy Clin Immunol 1988; 81:776-781.

3. Dvorak A, Ackerman S, Furitsu T, Estrella P, Letourneau L, Ishizaka T. Mature eosinophils stimulated to develop in human-cord blood mononuclear cell cultures supplemented with recombinant human interleukin-5. Am J Pathol 1992; 140:795-807.

4. Costa J, Weller P, Galli S. The cells of the allergic response. Mast cells, basophils, and eosinophils. JAMA 1997; 278:1815-1822.

5. Dvorak A, Ackerman S. Ultrastructural localization of the Charcot-Leyden crystal protein (lysophospholipase) to granules and intragranular crystals in mature human basophils. Lab Invest 1989; 60:557-567.

6. Golightly L, Thomas L, Dvorak A, Ackerman S. Charcot-Leyden crystal protein in the degranulation and recovery of activated basophils. J Leukoc Biol 1992; 51:386-392.

Clinical summary Image 6

Table of Contents