Eosinophils in the 1990s: New perspectives on their role in health and disease

Abstract

Summary Eosinophils are characterized by their unique crystalloid granules that contain four basic proteins--MBP, ECP, EDN and EPO. The cell has many common features with neutrophils but, unlike that cell type, eosinophils utilize VLA-4/VCAM-1 as an adherence pathway and have a number of other receptors not shared by neutrophils. These include recognition units for IgE (distinct from CD23), and receptors for IL-5, IL-3 and RANTES. Following stimulation with a variety of agents, eosinophils preferentially elaborate LTC4 as the major 5-lipoxygenase product of arachidonic acid and produce substantial amounts of PAF. Of particular interest is the ability of eosinophils to synthesize a number of cytokines. Thus eosinophils have marked pro-inflammatory potential. There is now convincing evidence that eosinophilia is T-cell dependent. The Th2-type cell, which selectively secretes IL-5 and IL-4, seems particularly involved. IL-5, IL-3 and GM-CSF are required for eosinophil maturation, and cause activation and prolonged survival of the mature cell. IL-5 is unique in that it promotes terminal differentiation of the committed eosinophil precursor and in vivo in mice appears to be sufficient on its own for eosinophil growth from uncommited stem cells. IL-4 selectively upregulates VCAM-1 expression on endothelial cells thus augmenting VLA-4-dependent eosinophil adhesion. The role of eosinophils in disease is complex but in general their numbers are increased in helminthic parasitic disease and atopic allergy and asthma. Eosinophil products can produce many of the pathological features of asthma, and helminthic larvae coated with immunoglobulin or complement are particularly susceptible to eosinophil-mediated cytotoxicity. Eosinopenia is often related to acute inflammation or stress.

Eosinophilia in patients infected with the human immunodeficiency virus

“…The occurrence of peripheral blood eosinophilia in patients with human immunodeficiency type 1 (HIV-1) infection has been described previously (1)(2)(3)(4). Our daily clinical work suggested that eosinophilia is more common in late-stage infection.…”

Caspase activation in the absence of mitochondrial changes in granulocyte apoptosis

“…Both cell types are key effector cells in host defence against infections and they contain and can, upon activation, secrete a large and varied armoury of cytotoxic and degenerative enzymes [1,2]. Eosinophils are most commonly involved in parasitic infections and allergic inflammation, where eosinophilia is a prevalent indication of late-phase allergic inflammation causing tissue damage and asthma severity [3]. Neutrophils, on the other hand, are mainly involved in bacterial infections and other inflammatory reactions [4].…”

Recent advances in pathogenesis and management of hypereosinophilic syndromes

“…Whatever its cause, eosinophil accumulation is deleterious and may in itself have pathological consequences as a result of local release of toxic substances, including cationic proteins, enzymes, reactive oxygen species, proinflammatory cytokines and arachidonic acid-derived factors (6).…”

“…Eosinophils are derived from myeloid progenitors (GEMM-CFU) in bone marrow, through the action of three hematopoietic cytokines, GM-CSF, interleukin (IL)-3, and IL-5, among which only the latter is specific for eosinophil differentiation (6). Mature eosinophils are released into the blood stream and rapidly migrate to peripheral tissues, namely gut and bronchial mucosae and skin, where survival is short unless apoptosis is prevented by factors such as IL-3, IL-5, and/or GM-CSF.…”