Neutrophil Extracellular Traps Drive Dacryolithiasis.
Leticija Zlatar1,2, Thomas Timm3, Günter Lochnit3
1Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Cells
|July 29, 2023
Summary
Neutrophils and neutrophil extracellular traps (NETs) play key roles in the formation of dacryoliths (mucopeptide concretions). Neutrophils are involved in early stages, while NETs contribute to later stages, impacting lacrimal sac obstruction.
Area of Science:
- Ophthalmology
- Immunology
- Pathology
Background:
- Mucopeptide concretions, or dacryoliths, obstruct the lacrimal sac, but their formation mechanism is not fully understood.
- While neutrophil involvement is known, the role of neutrophil extracellular traps (NETs) in dacryolithiasis is unexplored.
- NETs are implicated in other stone-forming diseases, suggesting a potential role in lacrimal sac pathology.
Purpose of the Study:
- To investigate the involvement of neutrophils and NETs in the pathogenesis of dacryolithiasis.
- To characterize mucopeptide concretions based on their composition.
- To elucidate the sequential roles of innate and adaptive immune components in dacryolith formation.
Main Methods:
- Microcomputed tomography and magnetic resonance tomography for structural analysis.
- Histochemistry, mass spectrometry, and enzyme activity assays for compositional and functional analysis.
- Immunohistochemistry to localize neutrophils and NETs within dacryoliths.
Main Results:
- Mucopeptide concretions were classified into three types based on cellular and acellular material, polysaccharides, and mucosubstances.
- Neutrophils were found in the inner, older parts of the concretions, suggesting early-stage involvement.
- NETs were localized in the outer, newer parts, indicating a role in later stages and potentially hindering clearance.
- Abundant IgG on the surface suggests adaptive immune system involvement in later stages.
Conclusions:
- Neutrophils and NETs are integral to the gradual formation and growth of mucopeptide concretions.
- Neutrophils contribute to the initial stages, while NETs are associated with later stages, possibly perpetuating inflammation.
- Both innate (neutrophils, NETs) and adaptive (IgG) immune systems are significantly involved in dacryolithiasis, offering new insights into the disease.
