Eosinophils

Published on 22/03/2015 by admin

Last modified 22/03/2015

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Chapter 123 Eosinophils

Eosinophils are distinguished from other leukocytes by their morphology, constituent products, and association with specific diseases. Eosinophils are nondividing fully-differentiated cells with a diameter of ≈8 µm and a bilobed nucleus. They differentiate from stem cell precursors in the bone marrow under the control of T cell–derived interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and, especially, IL-5. Their characteristic membrane-bound specific granules stain reddish brown with eosin and consist of a crystalline core made up of major basic protein (MBP) surrounded by a matrix containing the eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN). These basic proteins are cytotoxic for the larval stages of helminthic parasites such as Schistosoma mansoni and are also thought to contribute to much of the inflammation associated with asthma, causing sloughing of epithelial cells and contributing to clinical dysfunction (Chapter 138).

Both eosinophil MBP and ECP are also present in large quantities in the airways of patients who have died of asthma and are thought to inflict epithelial cell damage leading to airway hyperresponsiveness. Eosinophil granule contents also contribute to Loeffler endocarditis associated with hypereosinophilic syndrome. MBP has the potential to activate other proinflammatory cells, including mast cells, basophils, neutrophils, and platelets. Eosinophils have the capacity to generate large amounts of the lipid mediators platelet-activating factor and leukotriene-C4, both of which can cause vasoconstriction, smooth muscle contraction, and mucus hypersecretion. Eosinophils are a source of a number of proinflammatory cytokines, including IL-1, IL-3, IL-4, IL-5, IL-9, IL-13, and GM-CSF; they can also function as antigen-presenting cells. Thus, eosinophils have considerable potential to initiate and sustain inflammatory response of the innate and acquired immune systems.

Eosinophil migration from the vasculature into the extracellular tissue is mediated by the binding of leukocyte adhesion receptors to their ligands or counterstructures on the postcapillary endothelium. Similar to neutrophils (see Fig. 121-2), transmigration begins as the eosinophil selectin receptor binds to the endothelial carbohydrate ligand in loose association, which promotes eosinophils rolling along the endothelial surface until they encounter a priming stimulus such as a chemotactic mediator. Eosinophils then establish a high-affinity bond between integrin receptors and their corresponding immunoglobulin-like ligand. Unlike neutrophils, which become flattened before transmigrating between the tight junctions of the endothelial cells, eosinophils can use unique integrins, known as VLA-4, to bind to vascular cell adhesion molecule (VCAM)-1, which enhances eosinophil adhesion and transmigration through endothelium. Eosinophils are recruited to tissues in inflammatory states by the chemokine eotaxin. These unique pathways account for selective accumulation of eosinophils in allergic and inflammatory disorders. Eosinophils normally dwell primarily in tissues, especially tissues with an epithelial interface with the environment, including the respiratory, gastrointestinal, and lower genitourinary tracts. The life span of eosinophils may extend for weeks within tissues.

IL-5 selectively enhances eosinophil production, adhesion to endothelial cells, and function. Considerable evidence shows that IL-5 has a pivotal role in promoting eosinophil accumulation. It is the predominant cytokine in allergen-induced pulmonary late-phase reaction, and antibodies against IL-5 block eosinophil infiltration into the lungs in animal models associated with airway hyperresponsiveness following allergen challenge. Eosinophils also bear unique receptors for several chemokines, including RANTES, eotaxin, monocyte chemotactic protein (MCP)–3, and MCP-4. These chemokines appear to be key mediators in the induction of tissue eosinophilia.

Blood eosinophil numbers do not always reflect the extent of eosinophil involvement in disease-affected tissues. Eosinopenia occurs after corticosteroid administration and with some bacterial and viral infections.