Aggregated neutrophil extracellular traps occlude Meibomian glands during ocular surface inflammation

Mahajan, Aparna; Hasíková, Lenka; Hampel, Ulrike; Grüneboom, Anika; Shan, Xiaomei; Herrmann, I; Garreis, Fabian; Bock, Felix; Knopf, Jasmin; Singh, Jeeshan; Schauer, Christine; Mahajan, Siddharth; Leppkes, Moritz; Paulsen, Friedrich; Schlötzer‐Schrehardt, Ursula; Krenn, Veit; Jünemann, Anselm; Hohberger, Bettina; Schett, Georg; Herrmann, Martin; Muñoz, Luis E.

doi:10.1016/j.jtos.2020.12.005

Cited by 38 publications

(34 citation statements)

References 53 publications

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“…In a recent study, NETs were found in the ocular discharge of patients with blepharitis, and extensive aggregation of NETs were found in the meibomian glands [48]. In addition, in a murine model of allergic eye disease, it has been shown that NETs accumulate in the meibomian glands, obstructing the ducts and causing meibum retention and subsequent acinar atrophy [48]. Although histopathological investigation of meibomian glands could not be performed in our case, based on the results of these recent studies, we believe that aggregated NETs might have caused MGD in this case.…”

Section: Discussionmentioning

confidence: 95%

“…In ANCA-associated vasculitis, neutrophil extracellular traps (NETs), a bactericidal mechanism of neutrophils, have been shown to promote myeloperoxidase-ANCA production, thrombosis, inflammation and fibrosis, leading to a vicious cycle of inflammatory tissue changes [44][45][46][47]. In a recent study, NETs were found in the ocular discharge of patients with blepharitis, and extensive aggregation of NETs were found in the meibomian glands [48]. In addition, in a murine model of allergic eye disease, it has been shown that NETs accumulate in the meibomian glands, obstructing the ducts and causing meibum retention and subsequent acinar atrophy [48].…”

Section: Discussionmentioning

confidence: 99%

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Atypical Granulomatosis with Polyangiitis Presenting with Meibomitis, Scleritis, Uveitis and Papillary Bladder Tumor: A Case Report and Literature Review

et al. 2021

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Granulomatosis with polyangiitis (GPA) presents with a variety of systemic findings, sometimes with ocular findings initially, but is often difficult to diagnose at an early stage. An 85-year-old male had complaints of ocular dryness and redness and was diagnosed with meibomian gland dysfunction with meibomitis. Despite an initial treatment with topical steroid and antibiotics, the meibomitis did not improve and the left eye developed scleritis and iridocyclitis. The patient was administered topical mydriatics and oral steroids. During follow-up, the patient developed left hearing difficulty and reported a darker urine. Urinalysis revealed microscopic hematuria. A blood test showed an elevated erythrocyte sedimentation rate, positivity for perinuclear anti-neutorophil cytoplasmic antibody, and elevations in blood urea nitrogen and serum creatinine. Nasal mucosal biopsy showed a non-necrotizing granulomatous inflammation. Renal biopsy revealed focal glomerulosclerosis. Cystoscopy and bladder wash followed by a planned transurethral resection revealed atypical cells and apical papillary tumors which were resected. Iridocyclitis and scleritis responded well to oral prednisolone with 0.1% topical betamethasone and prednisolone ointment. The patient is tumor free with no recurrences 24 months after resection. GPA may present atypically with meibomian gland dysfunction without showing representative clinical findings. Early detection and treatment are essential for visual recovery.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Atypical Granulomatosis with Polyangiitis Presenting with Meibomitis, Scleritis, Uveitis and Papillary Bladder Tumor: A Case Report and Literature Review

et al. 2021

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“…The increased abundance of NETs in the tears and on the ocular surfaces of the patients with MGD and the positive correlation between NETs amounts and disease severity has reinforced this suspicion [ 84 ]. Although aggNETs have been known for their ability to resolve inflammation on the ocular surface [ 85 ], a recent study demonstrated that NETs are also implicated in MG terminal duct occlusions precipitating the inflammation on the ocular surface [ 9 ]. This work has provided vital new evidence to propose novel avenues in the treatment of MG occlusion-related disorders.…”

Section: Occlusions Of Exocrine Glands and Ductsmentioning

confidence: 99%

“…This makes PAD4 a possible therapeutic target for the treatment of occlusive NETs-related diseases. The increased activity of PAD4 and the therapeutic potential of its inhibition have already been reported in preclinical settings for the formation of thrombosis [ 22 ], acute pancreatitis [ 81 ], cholelithiasis [ 94 ], meibomian gland disfunction [ 9 ], lung injury [ 64 ], and sickle cell disease [ 56 ].…”

Section: Therapeutic Approaches To Prevent Nets-driven Occlusionsmentioning

confidence: 99%

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Neutrophil Extracellular Trap-Driven Occlusive Diseases

Yaykaşlı

Schauer

Muñoz

et al. 2021

Cells

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The enlightenment of the formation of neutrophil extracellular traps (NETs) as a part of the innate immune system shed new insights into the pathologies of various diseases. The initial idea that NETs are a pivotal defense structure was gradually amended due to several deleterious effects in consecutive investigations. NETs formation is now considered a double-edged sword. The harmful effects are not limited to the induction of inflammation by NETs remnants but also include occlusions caused by aggregated NETs (aggNETs). The latter carries the risk of occluding tubular structures like vessels or ducts and appear to be associated with the pathologies of various diseases. In addition to life-threatening vascular clogging, other occlusions include painful stone formation in the biliary system, the kidneys, the prostate, and the appendix. AggNETs are also prone to occlude the ductal system of exocrine glands, as seen in ocular glands, salivary glands, and others. Last, but not least, they also clog the pancreatic ducts in a murine model of neutrophilia. In this regard, elucidating the mechanism of NETs-dependent occlusions is of crucial importance for the development of new therapeutic approaches. Therefore, the purpose of this review is to address the putative mechanisms of NETs-associated occlusions in the pathogenesis of disease, as well as prospective treatment modalities.

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Nanoparticles for stimulation of neutrophil extracellular trap‐mediated immunity

Vaseruk,

Bila,

Bilyy

2024

Eur J Immunol

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Neutrophil extracellular traps (NETs) have been identified as triggers for a self‐limited inflammatory reaction upon contact with nanoparticles within our bodies. This typically results in entrapping potentially harmful nano‐ or micro‐objects following an immune burst. The demand for potent adjuvants has led to research on particulate‐based adjuvants, particularly those that act via NET formation. Various particles, including hydrophobic nanoparticles, needle‐like microparticles, and other natural and artificial crystals, have been shown to induce NET formation, eliciting a robust humoral and cellular immune response toward co‐injected antigens. The NET formation was found to be the basis of the efficient use of alum as a vaccine adjuvant. Thus, nanoparticles with specific surface properties serve as NET‐stimulating adjuvants. In this mini‐review, we aim to summarize the current knowledge about the surface properties of particulate objects and the molecular pathways involved in inducing NET formation by neutrophils. Additionally, we discuss the potential use of nanoparticles for activating neutrophils in the tissues and the exploitation of such activation for enhancing vaccine adjuvants.

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Aggregated neutrophil extracellular traps occlude Meibomian glands during ocular surface inflammation

Cited by 38 publications

References 53 publications

Atypical Granulomatosis with Polyangiitis Presenting with Meibomitis, Scleritis, Uveitis and Papillary Bladder Tumor: A Case Report and Literature Review

Atypical Granulomatosis with Polyangiitis Presenting with Meibomitis, Scleritis, Uveitis and Papillary Bladder Tumor: A Case Report and Literature Review

Neutrophil Extracellular Trap-Driven Occlusive Diseases

Nanoparticles for stimulation of neutrophil extracellular trap‐mediated immunity

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