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Aggregated eosinophils and neutrophils characterize the properties of mucus in chronic rhinosinusitis - 03/05/24

Doi : 10.1016/j.jaci.2023.11.925 
Yui Miyabe, MD, PhD a, b, Mineyo Fukuchi, MD, PhD a, Hiroki Tomizawa, MD a, b, Yuka Nakamura, MD, PhD a, Mitsutoshi Jikei, MD, PhD c, Yoshinori Matsuwaki, MD, PhD d, Misaki Arima, DDS a, Yasunori Konno, DDS, PhD a, Yuki Moritoki, MD, PhD a, Masahide Takeda, MD, PhD a, Naoya Tanabe, MD, PhD e, Hiroshi Shima, MD, PhD e, Yusuke Shiraishi, MD, PhD e, Toyohiro Hirai, MD, PhD e, Nobuo Ohta, MD, PhD f, Junko Takahata, MD, PhD g, Atsushi Matsubara, MD, PhD g, Takechiyo Yamada, MD, PhD b, Koichiro Asano, MD, PhD h, Isao Miyairi, MD, PhD i, Rossana C.N. Melo, PhD j, Peter F. Weller, MD k, Shigeharu Ueki, MD, PhD a,
a Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan 
b Department of Otorhinolaryngology Head and Neck Surgery, Akita University Graduate School of Medicine, Akita, Japan 
c Department of Materials Science, Akita University Graduate School of Engineering Science, Akita, Japan 
d Matsuwaki Clinic Shinagawa, Shinagawa, Tokyo, Japan 
e Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan 
f Department of Otolaryngology, Tohoku Medical and Pharmaceutical University, Sendai, Japan 
g Department of Otorhinolaryngology–Head and Neck Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan 
h Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Japan 
i Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan 
j Laboratory of Cellular Biology, Department of Biology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, Brazil 
k Divisions of Allergy and Inflammation and Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass 

Corresponding author: Shigeharu Ueki, MD, PhD, Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.Department of General Internal Medicine and Clinical Laboratory MedicineAkita University Graduate School of Medicine1-1-1 HondoAkita010-8543Japan

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Abstract

Background

Airway obstruction caused by viscous mucus is an important pathophysiologic characteristic of persistent inflammation, which can result in organ damage.

Objective

We investigated the hypothesis that the biophysical characteristics of accumulating granulocytes affect the clinical properties of mucus.

Methods

Surgically acquired nasal mucus samples from patients with eosinophilic chronic rhinosinusitis and neutrophil-dominant, noneosinophilic chronic rhinosinusitis were evaluated in terms of computed tomography density, viscosity, water content, wettability, and protein composition. Isolated human eosinophils and neutrophils were stimulated to induce the formation of extracellular traps, followed by the formation of aggregates. The biophysical properties of the aggregated cells were also examined.

Results

Mucus from patients with eosinophilic chronic rhinosinusitis had significantly higher computed tomography density, viscosity, dry weight, and hydrophobicity compared to mucus from patients with noneosinophilic chronic rhinosinusitis. The levels of eosinophil-specific proteins in mucus correlated with its physical properties. Eosinophil and neutrophil aggregates showed physical and pathologic characteristics resembling those of mucus. Cotreatment with deoxyribonuclease and heparin, which slenderizes the structure of eosinophil extracellular traps, efficiently induced reductions in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus.

Conclusions

The present study elucidated the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a novel perspective. These findings may contribute to the development of treatment strategies for eosinophilic airway diseases.

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Key words : Eosinophils, extracellular traps, chronic rhinosinusitis, mucus, neutrophils

Abbreviations used : aggEETs, aggNETs, CT, DNase, ECRS, EDN, EETs, ET, ETosis, JESREC, MPO, NETs, TGA


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Vol 153 - N° 5

P. 1306-1318 - mai 2024 Retour au numéro
Article précédent Article précédent
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