Neutrophil extracellular traps and active myeloperoxidase concentrate in lamellar tissue of equids with naturally occurring laminitis.
Authors: N. Storms, G. de la Rebière, T. Franck, Ange Mouithys Mickalad, C. Sandersen, J. Ceusters, D. Serteyn
Journal: Veterinary immunology and immunopathology
Summary
# Editorial Summary Neutrophil extracellular traps (NETs) and myeloperoxidase (MPO) activity have been implicated in experimentally-induced laminitis, but whether they contribute to naturally occurring disease remained unclear. Storms and colleagues examined lamellar tissue from five horses and five donkeys with clinical laminitis alongside eight healthy control horses, using ELISA and immunohistochemical techniques to quantify both total MPO levels and NET-bound MPO activity. Laminitis cases showed significantly elevated total MPO concentration, MPO activity, and NET-bound MPO activity compared with controls, with a strong correlation observed between NET-bound and total MPO activity—indicating that NETs are a substantial source of damaging oxidative enzymes in affected lamellae. Immunohistological staining confirmed moderate to marked MPO and NET labelling predominantly within the epidermal layer and neutrophil-rich inflammatory infiltrates of laminitis cases, whilst control tissue showed minimal staining. These findings provide the first direct evidence that NET-associated inflammation contributes to naturally occurring equine and donkey laminitis, potentially opening therapeutic avenues targeting neutrophil activation and NET formation as adjunctive or preventative strategies in this economically and welfare-significant condition.
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Practical Takeaways
- •Neutrophil extracellular traps and their enzymatic activity represent a previously unrecognized pathogenic mechanism in naturally occurring laminitis that may be therapeutically targetable
- •The significant presence of NET-bound myeloperoxidase in lamellar tissue suggests that anti-inflammatory or neutrophil-modulating treatments could potentially offer new treatment options for laminitis cases
- •This research provides foundational evidence for developing novel therapeutic interventions aimed at reducing neutrophil activation and NET formation as adjunctive treatment for laminitis
Key Findings
- •Laminitis cases showed significantly higher levels of total myeloperoxidase (MPO) concentration, MPO activity, and neutrophil extracellular trap (NET)-bound MPO activity compared to control horses
- •Strong correlation identified between NET-bound MPO activity and total MPO activity, indicating that MPO activity partly originates from NET-bound sources
- •Immunohistochemical staining revealed moderate to marked MPO and NET labelling primarily in the epidermis and inflammatory infiltrates of laminitis cases, with minimal labelling in controls
- •Both horses and donkeys with naturally occurring laminitis showed comparable patterns of NET and active MPO accumulation in lamellar tissue