Neutrophil extracellular traps in nasal secretions of patients with stable and exacerbated chronic rhinosinusitis and their contribution to induce chemokine secretion and strengthen the epithelial barrier

Jae Woong Hwang, Jae Hyung Kim, Hyun Jung Kim, In Hak Choi, Hye Min Han, Ki Jung Lee, Tae-Hoon Kim, Sang Hag Lee

Research output: Contribution to journalArticle

Abstract

Background: Neutrophil extracellular traps (NETs) participate in innate immunity by trapping microorganisms. Their pathophysiological implications have not been defined in chronic rhinosinusitis (CRS). Objective: We investigated the presence of NETs in nasal secretion of patients with stable or exacerbated CRS and evaluated whether NETs participate in the secretion of chemokines in sinonasal epithelial cells, the epithelial permeability, and transendothelial leucocyte migration, and elucidate whether NETs are released by macrolides and dexamethasone. Methods: The presence of NETs in nasal secretion and the release of NETs from neutrophils stimulated with macrolides or dexamethasone were evaluated by dsDNA Assay kit and fluorescence microscope. The chemokine secretion, epithelial permeability, and transendothelial leucocyte migration were measured in cultured cells incubated with NETs, the supernatant of unstimulated neutrophils (unstim), NETs inhibitor (DPI), or H3Cit, where the expression of junctional complex proteins and ICAM-1 was evaluated by real-time PCR, Western blots, and confocal microscope. Results: The amount of NETs and NETs-forming neutrophils in nasal secretion increased in exacerbated CRS. Epithelial cells treated with NETs or H3Cit secreted chemokines and showed decreased permeability associated with up-regulated junctional complex proteins. Increased transendothelial leucocyte migration associated with up-regulated ICAM-1 was noted in endothelial cells treated with NETs or H3Cit. These findings were not found in cells treated with unstim, or DPI. NETs were released by macrolides, but not by dexamethasone. Conclusions and Clinical Relevance: NETs formation increased in exacerbated CRS, inducing chemokine secretion, strengthening the epithelial barrier, and promoting the neutrophils infiltration. Therefore, the release of NETs in CRS might be beneficial or detrimental to CRS patients.

Original languageEnglish
JournalClinical and Experimental Allergy
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Nose
Chemokines
Transendothelial and Transepithelial Migration
Macrolides
Neutrophils
Dexamethasone
Permeability
Leukocytes
Extracellular Traps
Intercellular Adhesion Molecule-1
Epithelial Cells
Neutrophil Infiltration
Innate Immunity
Real-Time Polymerase Chain Reaction
Cultured Cells
Proteins
Endothelial Cells
Fluorescence
Western Blotting

Keywords

  • chemokines
  • dexamethasone
  • epithelial permeability
  • macrolides
  • neutrophil extracellular traps
  • transendothelial leucocyte migration

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{fc5abcab8f0e45219d9a38f19d743f03,
title = "Neutrophil extracellular traps in nasal secretions of patients with stable and exacerbated chronic rhinosinusitis and their contribution to induce chemokine secretion and strengthen the epithelial barrier",
abstract = "Background: Neutrophil extracellular traps (NETs) participate in innate immunity by trapping microorganisms. Their pathophysiological implications have not been defined in chronic rhinosinusitis (CRS). Objective: We investigated the presence of NETs in nasal secretion of patients with stable or exacerbated CRS and evaluated whether NETs participate in the secretion of chemokines in sinonasal epithelial cells, the epithelial permeability, and transendothelial leucocyte migration, and elucidate whether NETs are released by macrolides and dexamethasone. Methods: The presence of NETs in nasal secretion and the release of NETs from neutrophils stimulated with macrolides or dexamethasone were evaluated by dsDNA Assay kit and fluorescence microscope. The chemokine secretion, epithelial permeability, and transendothelial leucocyte migration were measured in cultured cells incubated with NETs, the supernatant of unstimulated neutrophils (unstim), NETs inhibitor (DPI), or H3Cit, where the expression of junctional complex proteins and ICAM-1 was evaluated by real-time PCR, Western blots, and confocal microscope. Results: The amount of NETs and NETs-forming neutrophils in nasal secretion increased in exacerbated CRS. Epithelial cells treated with NETs or H3Cit secreted chemokines and showed decreased permeability associated with up-regulated junctional complex proteins. Increased transendothelial leucocyte migration associated with up-regulated ICAM-1 was noted in endothelial cells treated with NETs or H3Cit. These findings were not found in cells treated with unstim, or DPI. NETs were released by macrolides, but not by dexamethasone. Conclusions and Clinical Relevance: NETs formation increased in exacerbated CRS, inducing chemokine secretion, strengthening the epithelial barrier, and promoting the neutrophils infiltration. Therefore, the release of NETs in CRS might be beneficial or detrimental to CRS patients.",
keywords = "chemokines, dexamethasone, epithelial permeability, macrolides, neutrophil extracellular traps, transendothelial leucocyte migration",
author = "Hwang, {Jae Woong} and Kim, {Jae Hyung} and Kim, {Hyun Jung} and Choi, {In Hak} and Han, {Hye Min} and Lee, {Ki Jung} and Tae-Hoon Kim and Lee, {Sang Hag}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/cea.13448",
language = "English",
journal = "Clinical and Experimental Allergy",
issn = "0954-7894",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Neutrophil extracellular traps in nasal secretions of patients with stable and exacerbated chronic rhinosinusitis and their contribution to induce chemokine secretion and strengthen the epithelial barrier

AU - Hwang, Jae Woong

AU - Kim, Jae Hyung

AU - Kim, Hyun Jung

AU - Choi, In Hak

AU - Han, Hye Min

AU - Lee, Ki Jung

AU - Kim, Tae-Hoon

AU - Lee, Sang Hag

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Neutrophil extracellular traps (NETs) participate in innate immunity by trapping microorganisms. Their pathophysiological implications have not been defined in chronic rhinosinusitis (CRS). Objective: We investigated the presence of NETs in nasal secretion of patients with stable or exacerbated CRS and evaluated whether NETs participate in the secretion of chemokines in sinonasal epithelial cells, the epithelial permeability, and transendothelial leucocyte migration, and elucidate whether NETs are released by macrolides and dexamethasone. Methods: The presence of NETs in nasal secretion and the release of NETs from neutrophils stimulated with macrolides or dexamethasone were evaluated by dsDNA Assay kit and fluorescence microscope. The chemokine secretion, epithelial permeability, and transendothelial leucocyte migration were measured in cultured cells incubated with NETs, the supernatant of unstimulated neutrophils (unstim), NETs inhibitor (DPI), or H3Cit, where the expression of junctional complex proteins and ICAM-1 was evaluated by real-time PCR, Western blots, and confocal microscope. Results: The amount of NETs and NETs-forming neutrophils in nasal secretion increased in exacerbated CRS. Epithelial cells treated with NETs or H3Cit secreted chemokines and showed decreased permeability associated with up-regulated junctional complex proteins. Increased transendothelial leucocyte migration associated with up-regulated ICAM-1 was noted in endothelial cells treated with NETs or H3Cit. These findings were not found in cells treated with unstim, or DPI. NETs were released by macrolides, but not by dexamethasone. Conclusions and Clinical Relevance: NETs formation increased in exacerbated CRS, inducing chemokine secretion, strengthening the epithelial barrier, and promoting the neutrophils infiltration. Therefore, the release of NETs in CRS might be beneficial or detrimental to CRS patients.

AB - Background: Neutrophil extracellular traps (NETs) participate in innate immunity by trapping microorganisms. Their pathophysiological implications have not been defined in chronic rhinosinusitis (CRS). Objective: We investigated the presence of NETs in nasal secretion of patients with stable or exacerbated CRS and evaluated whether NETs participate in the secretion of chemokines in sinonasal epithelial cells, the epithelial permeability, and transendothelial leucocyte migration, and elucidate whether NETs are released by macrolides and dexamethasone. Methods: The presence of NETs in nasal secretion and the release of NETs from neutrophils stimulated with macrolides or dexamethasone were evaluated by dsDNA Assay kit and fluorescence microscope. The chemokine secretion, epithelial permeability, and transendothelial leucocyte migration were measured in cultured cells incubated with NETs, the supernatant of unstimulated neutrophils (unstim), NETs inhibitor (DPI), or H3Cit, where the expression of junctional complex proteins and ICAM-1 was evaluated by real-time PCR, Western blots, and confocal microscope. Results: The amount of NETs and NETs-forming neutrophils in nasal secretion increased in exacerbated CRS. Epithelial cells treated with NETs or H3Cit secreted chemokines and showed decreased permeability associated with up-regulated junctional complex proteins. Increased transendothelial leucocyte migration associated with up-regulated ICAM-1 was noted in endothelial cells treated with NETs or H3Cit. These findings were not found in cells treated with unstim, or DPI. NETs were released by macrolides, but not by dexamethasone. Conclusions and Clinical Relevance: NETs formation increased in exacerbated CRS, inducing chemokine secretion, strengthening the epithelial barrier, and promoting the neutrophils infiltration. Therefore, the release of NETs in CRS might be beneficial or detrimental to CRS patients.

KW - chemokines

KW - dexamethasone

KW - epithelial permeability

KW - macrolides

KW - neutrophil extracellular traps

KW - transendothelial leucocyte migration

UR - http://www.scopus.com/inward/record.url?scp=85068896569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068896569&partnerID=8YFLogxK

U2 - 10.1111/cea.13448

DO - 10.1111/cea.13448

M3 - Article

C2 - 31183918

AN - SCOPUS:85068896569

JO - Clinical and Experimental Allergy

JF - Clinical and Experimental Allergy

SN - 0954-7894

ER -