Microparticles in nasal lavage fluids in chronic rhinosinusitis: Potential biomarkers for diagnosis of aspirin-exacerbated respiratory disease

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Abstract

Background Microparticles (MPs) are submicron-sized shed membrane vesicles released from activated or injured cells and are detectable by flow cytometry. MP levels have been used as biomarkers to evaluate cell injury or activation in patients with pathological conditions. Objective We sought to compare MP types and levels in nasal lavage fluids (NLFs) from controls and patients with chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD). Methods We collected NLFs from patients with CRSsNP (n = 33), CRSwNP (n = 45), and AERD (n = 31) and control (n = 24) subjects. Standardized flow cytometry methods were used to characterize the following MP types: endothelial MPs, epithelial MPs (epithelial cell adhesion molecule [EpCAM](+)MPs, E-cadherin(+)MPs), platelet MPs (CD31(+)CD41(+)MPs), eosinophil MPs (EGF-like module-containing mucin-like hormone receptor-like 1[EMR1](+)MPs), mast cell MPs (high-affinity IgE receptor [FcεRI](+)c-kit(+)MPs), and basophil MPs (CD203c(+)c-kit(−)MPs). Basophil activation was evaluated by the mean fluorescence intensity of CD203c on basophil MPs. Results Activated mast cell MPs (CD137(+) FcεRI(+)c-kit(+)MPs) were significantly increased in NLFs of controls compared with NLFs of patients with CRSsNP (2.3-fold; P < ·02), CRSwNP (2.3-fold; P < ·03), and AERD (7.4-fold; P < ·0001). Platelet MPs (3.5-fold; P < ·01) and basophil MPs (2.5-fold; P < ·05) were increased only in patients with AERD. Mean fluorescence intensity of CD203c on MPs was increased in patients with CRSwNP (P < ·002) and AERD (P < ·0001), but not in patients with CRSsNP. EpCAM(+)MPs in patients with CRSwNP were no different from control (P = ·91) and lower than those in patients with CRSsNP (P < ·02) and AERD (P < ·002). Conclusions Based on released MPs, mast cells, platelets, and basophils were more highly activated in patients with AERD than in patients with CRS. Epithelial injury was lower in patients with CRSwNP than in patients with CRSsNP and AERD. MP analysis may help identify phenotypes of CRS, and in distinguishing AERD from CRSwNP.

Original languageEnglish (US)
Pages (from-to)720-729
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume140
Issue number3
DOIs
StatePublished - Sep 1 2017

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Nasal Lavage Fluid
Nasal Polyps
Aspirin
Biomarkers
Basophils
Mast Cells
Blood Platelets
Flow Cytometry
Fluorescence
IgE Receptors
Wounds and Injuries
Mucins
Cadherins
Epidermal Growth Factor
Eosinophils

Keywords

  • CD137
  • CD69
  • Microparticles
  • apoptosis
  • aspirin-exacerbated respiratory disease
  • basophil activation
  • chronic rhinosinusitis
  • eosinophil activation
  • epithelial injury
  • mast cell activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{9a5a753461bc4149a35ca2cae1e714e6,
title = "Microparticles in nasal lavage fluids in chronic rhinosinusitis: Potential biomarkers for diagnosis of aspirin-exacerbated respiratory disease",
abstract = "Background Microparticles (MPs) are submicron-sized shed membrane vesicles released from activated or injured cells and are detectable by flow cytometry. MP levels have been used as biomarkers to evaluate cell injury or activation in patients with pathological conditions. Objective We sought to compare MP types and levels in nasal lavage fluids (NLFs) from controls and patients with chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD). Methods We collected NLFs from patients with CRSsNP (n = 33), CRSwNP (n = 45), and AERD (n = 31) and control (n = 24) subjects. Standardized flow cytometry methods were used to characterize the following MP types: endothelial MPs, epithelial MPs (epithelial cell adhesion molecule [EpCAM](+)MPs, E-cadherin(+)MPs), platelet MPs (CD31(+)CD41(+)MPs), eosinophil MPs (EGF-like module-containing mucin-like hormone receptor-like 1[EMR1](+)MPs), mast cell MPs (high-affinity IgE receptor [FcεRI](+)c-kit(+)MPs), and basophil MPs (CD203c(+)c-kit(−)MPs). Basophil activation was evaluated by the mean fluorescence intensity of CD203c on basophil MPs. Results Activated mast cell MPs (CD137(+) FcεRI(+)c-kit(+)MPs) were significantly increased in NLFs of controls compared with NLFs of patients with CRSsNP (2.3-fold; P < ·02), CRSwNP (2.3-fold; P < ·03), and AERD (7.4-fold; P < ·0001). Platelet MPs (3.5-fold; P < ·01) and basophil MPs (2.5-fold; P < ·05) were increased only in patients with AERD. Mean fluorescence intensity of CD203c on MPs was increased in patients with CRSwNP (P < ·002) and AERD (P < ·0001), but not in patients with CRSsNP. EpCAM(+)MPs in patients with CRSwNP were no different from control (P = ·91) and lower than those in patients with CRSsNP (P < ·02) and AERD (P < ·002). Conclusions Based on released MPs, mast cells, platelets, and basophils were more highly activated in patients with AERD than in patients with CRS. Epithelial injury was lower in patients with CRSwNP than in patients with CRSsNP and AERD. MP analysis may help identify phenotypes of CRS, and in distinguishing AERD from CRSwNP.",
keywords = "CD137, CD69, Microparticles, apoptosis, aspirin-exacerbated respiratory disease, basophil activation, chronic rhinosinusitis, eosinophil activation, epithelial injury, mast cell activation",
author = "Toru Takahashi and Atsushi Kato and Sergejs Berdnikovs and Stevens, {Whitney W.} and Suh, {Lydia A.} and Norton, {James E.} and Carter, {Roderick G.} and Harris, {Kathleen E.} and Peters, {Anju T.} and Hulse, {Kathryn E.} and Grammer, {Leslie C.} and Welch, {Kevin C.} and Stephanie Shintani-Smith and Tan, {Bruce K.} and Conley, {David B.} and Kern, {Robert C.} and Bochner, {Bruce S.} and Schleimer, {Robert P.}",
year = "2017",
month = "9",
day = "1",
doi = "10.1016/j.jaci.2017.01.022",
language = "English (US)",
volume = "140",
pages = "720--729",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Microparticles in nasal lavage fluids in chronic rhinosinusitis

T2 - Potential biomarkers for diagnosis of aspirin-exacerbated respiratory disease

AU - Takahashi, Toru

AU - Kato, Atsushi

AU - Berdnikovs, Sergejs

AU - Stevens, Whitney W.

AU - Suh, Lydia A.

AU - Norton, James E.

AU - Carter, Roderick G.

AU - Harris, Kathleen E.

AU - Peters, Anju T.

AU - Hulse, Kathryn E.

AU - Grammer, Leslie C.

AU - Welch, Kevin C.

AU - Shintani-Smith, Stephanie

AU - Tan, Bruce K.

AU - Conley, David B.

AU - Kern, Robert C.

AU - Bochner, Bruce S.

AU - Schleimer, Robert P.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Background Microparticles (MPs) are submicron-sized shed membrane vesicles released from activated or injured cells and are detectable by flow cytometry. MP levels have been used as biomarkers to evaluate cell injury or activation in patients with pathological conditions. Objective We sought to compare MP types and levels in nasal lavage fluids (NLFs) from controls and patients with chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD). Methods We collected NLFs from patients with CRSsNP (n = 33), CRSwNP (n = 45), and AERD (n = 31) and control (n = 24) subjects. Standardized flow cytometry methods were used to characterize the following MP types: endothelial MPs, epithelial MPs (epithelial cell adhesion molecule [EpCAM](+)MPs, E-cadherin(+)MPs), platelet MPs (CD31(+)CD41(+)MPs), eosinophil MPs (EGF-like module-containing mucin-like hormone receptor-like 1[EMR1](+)MPs), mast cell MPs (high-affinity IgE receptor [FcεRI](+)c-kit(+)MPs), and basophil MPs (CD203c(+)c-kit(−)MPs). Basophil activation was evaluated by the mean fluorescence intensity of CD203c on basophil MPs. Results Activated mast cell MPs (CD137(+) FcεRI(+)c-kit(+)MPs) were significantly increased in NLFs of controls compared with NLFs of patients with CRSsNP (2.3-fold; P < ·02), CRSwNP (2.3-fold; P < ·03), and AERD (7.4-fold; P < ·0001). Platelet MPs (3.5-fold; P < ·01) and basophil MPs (2.5-fold; P < ·05) were increased only in patients with AERD. Mean fluorescence intensity of CD203c on MPs was increased in patients with CRSwNP (P < ·002) and AERD (P < ·0001), but not in patients with CRSsNP. EpCAM(+)MPs in patients with CRSwNP were no different from control (P = ·91) and lower than those in patients with CRSsNP (P < ·02) and AERD (P < ·002). Conclusions Based on released MPs, mast cells, platelets, and basophils were more highly activated in patients with AERD than in patients with CRS. Epithelial injury was lower in patients with CRSwNP than in patients with CRSsNP and AERD. MP analysis may help identify phenotypes of CRS, and in distinguishing AERD from CRSwNP.

AB - Background Microparticles (MPs) are submicron-sized shed membrane vesicles released from activated or injured cells and are detectable by flow cytometry. MP levels have been used as biomarkers to evaluate cell injury or activation in patients with pathological conditions. Objective We sought to compare MP types and levels in nasal lavage fluids (NLFs) from controls and patients with chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD). Methods We collected NLFs from patients with CRSsNP (n = 33), CRSwNP (n = 45), and AERD (n = 31) and control (n = 24) subjects. Standardized flow cytometry methods were used to characterize the following MP types: endothelial MPs, epithelial MPs (epithelial cell adhesion molecule [EpCAM](+)MPs, E-cadherin(+)MPs), platelet MPs (CD31(+)CD41(+)MPs), eosinophil MPs (EGF-like module-containing mucin-like hormone receptor-like 1[EMR1](+)MPs), mast cell MPs (high-affinity IgE receptor [FcεRI](+)c-kit(+)MPs), and basophil MPs (CD203c(+)c-kit(−)MPs). Basophil activation was evaluated by the mean fluorescence intensity of CD203c on basophil MPs. Results Activated mast cell MPs (CD137(+) FcεRI(+)c-kit(+)MPs) were significantly increased in NLFs of controls compared with NLFs of patients with CRSsNP (2.3-fold; P < ·02), CRSwNP (2.3-fold; P < ·03), and AERD (7.4-fold; P < ·0001). Platelet MPs (3.5-fold; P < ·01) and basophil MPs (2.5-fold; P < ·05) were increased only in patients with AERD. Mean fluorescence intensity of CD203c on MPs was increased in patients with CRSwNP (P < ·002) and AERD (P < ·0001), but not in patients with CRSsNP. EpCAM(+)MPs in patients with CRSwNP were no different from control (P = ·91) and lower than those in patients with CRSsNP (P < ·02) and AERD (P < ·002). Conclusions Based on released MPs, mast cells, platelets, and basophils were more highly activated in patients with AERD than in patients with CRS. Epithelial injury was lower in patients with CRSwNP than in patients with CRSsNP and AERD. MP analysis may help identify phenotypes of CRS, and in distinguishing AERD from CRSwNP.

KW - CD137

KW - CD69

KW - Microparticles

KW - apoptosis

KW - aspirin-exacerbated respiratory disease

KW - basophil activation

KW - chronic rhinosinusitis

KW - eosinophil activation

KW - epithelial injury

KW - mast cell activation

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U2 - 10.1016/j.jaci.2017.01.022

DO - 10.1016/j.jaci.2017.01.022

M3 - Article

VL - 140

SP - 720

EP - 729

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -