Neutrophil Extracellular Traps Drive Dacryolithiasis

Cells. 2023 Jul 14;12(14):1857. doi: 10.3390/cells12141857.

Abstract

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.

Keywords: dacryolithiasis; dacryoliths; lacrimal sac; mucopeptide concretions; neutrophil extracellular traps; neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Extracellular Traps*
  • Humans
  • Lacrimal Apparatus Diseases* / pathology
  • Neutrophils / pathology
  • X-Ray Microtomography

Grants and funding

This work was partially supported by the Deutsche Forschungsgemeinschaft (DFG) 2886 PANDORA Project-No. B3 to MH, CRC1181-261193037 (C03) to MH, SFB/TRR 241 (B04) to MH, PA738/15-1 to FP, by the European Union H2020-FETOPEN-2018-2019-2020-01 to MH, by the European Commission 861878 ”NeutroCure” to MH, by the Volkswagen Foundation (Grant 97744) to MH and RB, and by the National Research Foundation of Ukraine grant 2020.02.0131 to RB. We acknowledge financial support from Deutsche Forschungsgemeinschaft and Friedrich-Alexander-Universität Erlangen-Nürnberg within the funding programme “Open Access Publication Funding”. The study was conducted in accordance with the Declaration of Helsinki, and approved by the ethical committee of the University Hospital Erlangen (permit 243_15 B).