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.
N1 - Publisher Copyright:
© 2017 American Academy of Allergy, Asthma & Immunology
PY - 2017/9
Y1 - 2017/9
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
C2 - 28238741
AN - SCOPUS:85016484365
SN - 0091-6749
VL - 140
SP - 720
EP - 729
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 3
ER -