Neutrophil Extracellular Traps Drive Dacryolithiasis

Mucopeptide concretions, previously called dacryoliths, are macroscopic stones that commonly obstruct the lacrimal sac. The mechanism behind dacryolithiasis remains unclear; however, the involvement of various immune cells, including neutrophils, has been confirmed. These findings remain limited, an...

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Main Authors: Leticija Zlatar, Thomas Timm, Günter Lochnit, Rostyslav Bilyy, Tobias Bäuerle, Marco Munoz-Becerra, Georg Schett, Jasmin Knopf, Jens Heichel, Mohammad Javed Ali, Mirco Schapher, Friedrich Paulsen, Martin Herrmann
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/12/14/1857
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author Leticija Zlatar
Thomas Timm
Günter Lochnit
Rostyslav Bilyy
Tobias Bäuerle
Marco Munoz-Becerra
Georg Schett
Jasmin Knopf
Jens Heichel
Mohammad Javed Ali
Mirco Schapher
Friedrich Paulsen
Martin Herrmann
author_facet Leticija Zlatar
Thomas Timm
Günter Lochnit
Rostyslav Bilyy
Tobias Bäuerle
Marco Munoz-Becerra
Georg Schett
Jasmin Knopf
Jens Heichel
Mohammad Javed Ali
Mirco Schapher
Friedrich Paulsen
Martin Herrmann
author_sort Leticija Zlatar
collection DOAJ
description Mucopeptide concretions, previously called dacryoliths, are macroscopic stones that commonly obstruct the lacrimal sac. The mechanism behind dacryolithiasis remains unclear; however, the involvement of various immune cells, including neutrophils, has been confirmed. These findings remain limited, and no information on neutrophil extracellular traps (NETs), essentially involved in the pathogenesis of other lithiases, is available yet. Here, we employ microcomputed tomography, magnetic resonance tomography, histochemistry, mass spectrometry, and enzyme activity analyses to investigate the role of neutrophils and NETs in dacryolithiasis. We classify mucopeptide concretions into three types, with respect to the quantity of cellular and acellular material, polysaccharides, and mucosubstances. We propose the role of neutrophils and NETs within the existing model of gradual formation and growth of mucopeptide concretions, with neutrophils contributing to the initial stages of dacryolithiasis, as they localized on the inner (older) parts of the tissue. As NETs localized on the outer (newer) parts of the tissue, we link their role to the late stages of dacryolithiasis, presumably maintaining the proinflammatory environment and preventing efficient clearance. An abundance of IgG on the surface indicates the involvement of the adaptive immune system later as well. These findings bring new perspectives on dacryolithiasis, in which the innate and adaptive immune system are essentially involved.
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spelling doaj.art-c803608be7a64b538967772af138df812023-11-18T18:46:10ZengMDPI AGCells2073-44092023-07-011214185710.3390/cells12141857Neutrophil Extracellular Traps Drive DacryolithiasisLeticija Zlatar0Thomas Timm1Günter Lochnit2Rostyslav Bilyy3Tobias Bäuerle4Marco Munoz-Becerra5Georg Schett6Jasmin Knopf7Jens Heichel8Mohammad Javed Ali9Mirco Schapher10Friedrich Paulsen11Martin Herrmann12Department of Internal Medicine 3—Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Biochemistry, Justus-Liebig University Giessen, 35392 Giessen, GermanyInstitute of Biochemistry, Justus-Liebig University Giessen, 35392 Giessen, GermanyDepartment of Histology, Cytology, Embryology, Danylo Halytsky Lviv National Medical University, 79010 Lviv, UkraineInstitute of Radiology, Preclinical Imaging Platform Erlangen (PIPE), Universitätsklinikum Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Internal Medicine 3—Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Internal Medicine 3—Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Internal Medicine 3—Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment and Policlinic of Ophthalmology, Martin Luther University of Halle-Wittenberg, 06108 Halle, GermanyGovindram Seksaria Institute of Dacryology, L.V. Prasad Eye Institute, Road No 2, Banjara Hills, Hyderabad 500034, IndiaDepartment of Otorhinolaryngology, Head and Neck Surgery, Universitätsklinikum Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Functional and Clinical Anatomy, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Internal Medicine 3—Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyMucopeptide concretions, previously called dacryoliths, are macroscopic stones that commonly obstruct the lacrimal sac. The mechanism behind dacryolithiasis remains unclear; however, the involvement of various immune cells, including neutrophils, has been confirmed. These findings remain limited, and no information on neutrophil extracellular traps (NETs), essentially involved in the pathogenesis of other lithiases, is available yet. Here, we employ microcomputed tomography, magnetic resonance tomography, histochemistry, mass spectrometry, and enzyme activity analyses to investigate the role of neutrophils and NETs in dacryolithiasis. We classify mucopeptide concretions into three types, with respect to the quantity of cellular and acellular material, polysaccharides, and mucosubstances. We propose the role of neutrophils and NETs within the existing model of gradual formation and growth of mucopeptide concretions, with neutrophils contributing to the initial stages of dacryolithiasis, as they localized on the inner (older) parts of the tissue. As NETs localized on the outer (newer) parts of the tissue, we link their role to the late stages of dacryolithiasis, presumably maintaining the proinflammatory environment and preventing efficient clearance. An abundance of IgG on the surface indicates the involvement of the adaptive immune system later as well. These findings bring new perspectives on dacryolithiasis, in which the innate and adaptive immune system are essentially involved.https://www.mdpi.com/2073-4409/12/14/1857mucopeptide concretionsdacryolithsdacryolithiasislacrimal sacneutrophilsneutrophil extracellular traps
spellingShingle Leticija Zlatar
Thomas Timm
Günter Lochnit
Rostyslav Bilyy
Tobias Bäuerle
Marco Munoz-Becerra
Georg Schett
Jasmin Knopf
Jens Heichel
Mohammad Javed Ali
Mirco Schapher
Friedrich Paulsen
Martin Herrmann
Neutrophil Extracellular Traps Drive Dacryolithiasis
Cells
mucopeptide concretions
dacryoliths
dacryolithiasis
lacrimal sac
neutrophils
neutrophil extracellular traps
title Neutrophil Extracellular Traps Drive Dacryolithiasis
title_full Neutrophil Extracellular Traps Drive Dacryolithiasis
title_fullStr Neutrophil Extracellular Traps Drive Dacryolithiasis
title_full_unstemmed Neutrophil Extracellular Traps Drive Dacryolithiasis
title_short Neutrophil Extracellular Traps Drive Dacryolithiasis
title_sort neutrophil extracellular traps drive dacryolithiasis
topic mucopeptide concretions
dacryoliths
dacryolithiasis
lacrimal sac
neutrophils
neutrophil extracellular traps
url https://www.mdpi.com/2073-4409/12/14/1857
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