Regulation of Eosinophil Mediator Release by Adhesion Molecules
Bruce S. Bochner in Adhesion Molecules in Allergic Disease, 2020
Eosinophil peroxidase differs from neutrophil or monocyte myeloperoxidase (MPO) in its absorption spectrum and its heme prosthetic groups (24). Analysis of EPO reveals the molecular masses of 12 and 53 kD for the heavy and light subunits, respectively; their calculated isoelectric points are 10.8 and 10.7, respectively (25). In the presence of H2O2, EPO is able to oxidize halides to form reactive hypohalous acids (26). Analyses of EPO’s halide preference shows that eosinophils preferentially utilize bromide over chloride (27). This EPO/H2O2/halide system kills a variety of microorganisms, such as schistosomula of S. mansoni and Escherichia coli (28,29). Studies of cultured human pneumocytes (30), nasal epithelial cells (31), and tumor cells (32) indicate that the EPO/H2O2/halide system causes toxicity to mammalian cells. Eosinophils by themselves can generate H2O2 (33) suggesting that this EPO/H2O2/halide system is an effective system to mediate toxicity toward numerous targets. In the absence of H2O2 and halide, EPO is also toxic to some targets although the activity seems somewhat limited. Eosinophil peroxidase, as well as MBP, is a potent stimulus for human platelets and eosinophils (14,15)
Mucosal basophils, eosinophils, and mast cells
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
The granules of eosinophils contain major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, and other enzymes of uncertain significance, as well as proteins that include a broad range of preformed cytokines and chemokines (Figure 14.4). Major basic protein is cytotoxic for helminthic parasites and mammalian cells, activates the complement cascade, and leads to increased smooth muscle reactivity by causing dysfunction of vagal muscarinic M2 receptors. Moreover, major basic protein has been shown to stimulate substance P release from neonatal rat dorsal root ganglia neurons. Eosinophil cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin induce cytotoxic effects in helminthic parasites and mammalian cells by exerting ribonuclease activity or generating unstable oxygen radicals. Among the cytokines and chemokines produced by eosinophils are IL-1α, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-16, interferon-γ (IFN-γ), GM-CSF, TNF-α, eotaxin (CCL11), IL-8 (CXCL8), macrophage inflammatory protein-1α (MIP-1α), RANTES (CCL5), nerve growth factor, stem cell factor (SCF), platelet-derived growth factor (PDGF), and transforming growth factor (TGF)-α and TGF-β1, among others.
Eosinophil Membrane Receptors: Function of IgE- and IgA-Binding Molecules
Gerald J. Gleich, A. Barry Kay in Eosinophils in Allergy and Inflammation, 2019
Effector functions of eosinophils against parasites, as well as against host cells, appear to be mainly mediated by the release of cationic proteins, such as major basic protein (MBP), eosinophil cationic protein (ECP), EDN, and eosinophil peroxidase (EPO). All these preformed mediators display a strong cytotoxic potential (27), but the precise mechanisms leading to eosinophil degranulation are still poorly understood. Studies on parasite-infected patients have shown that not all the granule proteins were simultaneously released after the same stimulus of activation, suggesting a differential release of EPO and ECP (28,29). It was not clear, however, whether eosinophils isolated from allergic patients could degranulate on exposure to allergens. To answer these questions, we have evaluated the release of EPO and ECP by eosinophils from allergic subjects, after the addition of the specific allergen or antihuman IgE MAb, in comparison to eosinophils from patients with eosinophilia of nonallergic origin. In addition, to further investigate the recently described interactions between IgA and human eosinophils (21,26), we have monitored the release of granule proteins after exposure of purified eosinophils to antihuman IgE, antihuman IgA, and antihuman IgG monoclonal antibodies and provided evidence that these three isotypes can be involved, although in different ways, in the antibody-dependent mechanisms of eosinophil activation (30).
Cysteinyl leukotriene induces eosinophil extracellular trap formation via cysteinyl leukotriene 1 receptor in a murine model of asthma
Published in Experimental Lung Research, 2021
Aline Andrea da Cunha, Josiane Silva Silveira, Géssica Luana Antunes, Keila Abreu da Silveira, Rodrigo Benedetti Gassen, Ricardo Vaz Breda, Paulo Márcio Pitrez
Asthma is a chronic inflammatory pulmonary disease with high morbidity and mortality worldwide. Pathophysiologic features of asthma include chronic inflammation in the airway, airway hyperresponsiveness (AHR), mucus overproduction, and variable obstruction associated with narrowing of the airway.1 In asthma, there is plasma extravasation, edema, and a high influx of inflammatory cells such as eosinophils, neutrophils, lymphocytes, macrophages, dendritic cells, and mast cells.2 However, eosinophils are key cells involved in the pathophysiology of asthma which increases lung dysfunction. In addition, eosinophils come equipped with preformed enzymatic and nonenzymatic cationic proteins, stored in and selectively secreted from their large secondary (specific) granules, such as eosinophil peroxidase (EPO). These proteins contribute to the functions of the eosinophil in airway inflammation and tissue damage.3
Blood eosinophils in COPD to predict exacerbations and inform inhaled corticosteroid use: Need for further evidence?
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2021
Most COPD sputum is characterized by CD8 T cell and neutrophil immune cell infiltration. In this patient population, ICSs are unlikely to produce any therapeutic benefit. However, airway eosinophils are also present in up to 20-40% of COPD patients, a situation paralleled by asthma, in which eosinophils are the overriding immune response.14 Eosinophils mature in the bone marrow before their release into circulation, where they only spend a brief time.15 Generally, they infiltrate and reside within tissue, though not lung tissue under normal physiological conditions, where their presence implicates a disease process. Interleukin-5 (IL-5), eotaxins and other cytokines, are the usual cue for eosinophils to penetrate into tissue. Activated eosinophils degranulate, releasing eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase and major basic protein that can increase inflammation and induce tissue damage and remodeling. However, the precise role of eosinophils in COPD, either as causative or correlative agents, is still uncertain.
Pharmacophore-based discovery of 2-(phenylamino)aceto-hydrazides as potent eosinophil peroxidase (EPO) inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Daniela Schuster, Martina Zederbauer, Thierry Langer, Andreas Kubin, Paul G. Furtmüller
Eosinophil peroxidase was purified from human white blood cells to a purity index (A413/A280) of at least 1.0 as described by Olsen and Little27. Its concentration was calculated using ε413 nm 110 000 M−1 cm−128 Hydrogen peroxide, obtained as a 30% solution from Sigma Chemical Co., was diluted and the concentration determined by the absorbance measurement at 240 nm where the extinction coefficient is 39.4 M−1 cm−129. The other chemicals were also purchased from Sigma Chemical Co. at the highest grade available.
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