Eosinophil peroxidase deficiency: morphological and immunocytochemical studies of the eosinophil-specific granules

Zabucchi, Giuliano; Soranzo, MR; Menegazzi, Renzo; Vecchio, Monica; Knowles, Alessandra; Piccinini, Clara; Spessotto, P; Patriarca, Pierluigi

doi:10.1182/blood.v80.11.2903.bloodjournal80112903

Cited by 5 publications

(5 citation statements)

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“…Thus, detection of these products in vivo, particularly during inflammatory conditions where eosinophils are abundant, would implicate a role for EPO in oxidative tissue damage. Although eosinophils are the only known cell type which synthesizes EPO, other phagocytic cells, such as neutrophils, mast cells, and basophils ( − ), have been shown to be capable of binding and internalizing this highly cationic protein, and may thus promote tissue injury through EPO-dependent formation of reactive brominating species. Furthermore, although MPO did not brominate protein tyrosine residues appreciably in the presence of plasma levels of Cl - and Br - (Figure ), this abundant leukocyte peroxidase may contribute to protein bromination, particularly at sites where Br - is abundant and Cl - is limiting.…”

Section: Discussionmentioning

confidence: 99%

3-Bromotyrosine and 3,5-Dibromotyrosine Are Major Products of Protein Oxidation by Eosinophil Peroxidase: Potential Markers for Eosinophil-Dependent Tissue Injury in Vivo

et al. 1999

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Detection of specific reaction products is a powerful approach for dissecting out pathways that mediate oxidative damage in vivo. Eosinophil peroxidase (EPO), an abundant protein secreted from activated eosinophils, has been implicated in promoting oxidative tissue injury in conditions such as asthma, allergic inflammatory disorders, cancer, and helminthic infections. This unique heme protein amplifies the oxidizing potential of H2O2 by utilizing plasma levels of Br- as a cosubstrate to form potent brominating agents. Brominated products might thus serve as powerful tools for identifying sites of eosinophil-mediated tissue injury in vivo; however, structural identification and characterization of specific brominated products formed during EPO-catalyzed oxidation have not yet been reported. Here we explore the role of EPO and myeloperoxidase (MPO), a related leukocyte protein, in promoting protein oxidative damage through bromination and demonstrate that protein tyrosine residues serve as endogenous traps of reactive brominating species forming stable ring-brominated adducts. Exposure of the amino acid L-tyrosine to EPO, H2O2, and physiological concentrations of halides (100 mM Cl-,

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Section: Discussionmentioning

confidence: 99%

3-Bromotyrosine and 3,5-Dibromotyrosine Are Major Products of Protein Oxidation by Eosinophil Peroxidase: Potential Markers for Eosinophil-Dependent Tissue Injury in Vivo

et al. 1999

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“…57 Berger et al 58 showed that multivesicular bodies from resting neutrophils express few LAMP vesicles, but they subsequently fuse with LAMP-positive structures, rendering them positive as well, and they then mature as prelysosomal compartments. 58 In related studies, the uptake of eosinophil peroxidase into vesicular structures in neutrophils was observed by Zabucchi et al 59 Of more relevance, Borregaard et al 16 showed that neutrophils contain endocytosed plasma proteins, particularly albumin, although this occurs mainly at the myelocyte stage of maturation.…”

Section: Lamp and Lysosomesmentioning

confidence: 90%

Azurophilic Granules of Human Neutrophilic Leukocytes Are Deficient in Lysosome-Associated Membrane Proteins but Retain the Mannose 6-Phosphate Recognition Marker

Cieutat

Lobel²,

August³

et al. 1998

Blood

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During granulocyte differentiation in the bone marrow (BM), neutrophilic leukocyte precursors synthesize large amounts of lysosomal enzymes. These enzymes are sequestered into azurophilic storage granules until used days later for digestion of phagocytized microorganisms after leukocyte emigration to inflamed tissues. This azurophil granule population has previously been defined as a primary lysosome, ie, a membrane-bound organelle containing acid hydrolases that have not entered into a digestive event. In this study, azurophil granules were purified and shown to contain large amounts of mannose 6-phosphate-containing glycoproteins (Man 6-P GP) but little lysosome-associated membrane proteins (LAMP). In addition, the fine structural localization of Man 6-P GP and LAMP was investigated at various stages of maturation in human BM and blood. Man 6-P GP were present within the azurophilic granules at all stages of maturation and in typical multivesicular bodies (MVB) as well as in multilaminar compartments (MLC), identified by their content of concentric arrays of internal membranes. LAMP was absent in all identified granule populations, but was consistently found in the membranes of vesicles, MVB, and MLC. The latter compartment has not been previously described in this cell type. In conclusion, the azurophilic granules, which contain an abundance of lysosomal enzymes and Man 6-P GP, lack the LAMP glycoproteins. By current criteria, they therefore cannot be classified as lysosomes, but rather may have the functional characteristics of a regulated secretory granule. Rather, the true lysosomes of the resting neutrophil are probably the MVB and MLC. Finally, the typical “dense bodies” or mature lysosomes described in other cells are not present in resting neutrophils.

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“…The clinical consequences of the eosinophil abnormalities in SGD are unknown. Abnormal eosinophil granule morphology without apparent clinical manifestations is also characteristic of the nearly 100 reported cases of hereditary eosinophil peroxidase deficiency (81).…”

Section: Eosinophil Deficiency In Humansmentioning

confidence: 94%

Contributions of Eosinophils to Human Health and Disease

Klion

Ackerman

Bochner

2020

Annu. Rev. Pathol. Mech. Dis.

170

178

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The human eosinophil has long been thought to favorably influence innate mucosal immunity but at times has also been incriminated in disease pathophysiology. Research into eosinophil biology has uncovered a number of interesting contributions by eosinophils to health and disease. However, it appears that not all eosinophils from all species are created equal. It remains unclear, for example, exactly how having eosinophils benefits the human host when helminth infections in the developed world have become scarce. This review focuses on our current state of knowledge as it relates to human eosinophils. When information is lacking, we discuss lessons learned from mouse studies that may or may not directly apply to human biology and disease. It is an exciting time to be an “eosinophilosopher” because the use of biologic agents that selectively target eosinophils provides an unprecedented opportunity to define the contribution of this cell to eosinophil-associated human diseases.

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Eosinophil peroxidase deficiency: morphological and immunocytochemical studies of the eosinophil-specific granules

Cited by 5 publications

References 1 publication

3-Bromotyrosine and 3,5-Dibromotyrosine Are Major Products of Protein Oxidation by Eosinophil Peroxidase: Potential Markers for Eosinophil-Dependent Tissue Injury in Vivo

3-Bromotyrosine and 3,5-Dibromotyrosine Are Major Products of Protein Oxidation by Eosinophil Peroxidase: Potential Markers for Eosinophil-Dependent Tissue Injury in Vivo

Azurophilic Granules of Human Neutrophilic Leukocytes Are Deficient in Lysosome-Associated Membrane Proteins but Retain the Mannose 6-Phosphate Recognition Marker

Contributions of Eosinophils to Human Health and Disease

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