Takahashi Toru, Kato Atsushi, Berdnikovs Sergejs, Stevens Whitney W, Suh Lydia A, Norton James E, Carter Roderick G, Harris Kathleen E, Peters Anju T, Hulse Kathryn E, Grammer Leslie C, Welch Kevin C, Shintani-Smith Stephanie, Tan Bruce K, Conley David B, Kern Robert C, Bochner Bruce S, Schleimer Robert P
Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
J Allergy Clin Immunol. 2017 Sep;140(3):720-729. doi: 10.1016/j.jaci.2017.01.022. Epub 2017 Feb 24.
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.
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).
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 EpCAMMPs, E-cadherin(+)MPs), platelet MPs (CD31(+)CD41(+)MPs), eosinophil MPs (EGF-like module-containing mucin-like hormone receptor-like 1EMR1MPs), mast cell MPs (high-affinity IgE receptor FcεRIc-kit(+)MPs), and basophil MPs (CD203c(+)c-kit(-)MPs). Basophil activation was evaluated by the mean fluorescence intensity of CD203c on basophil MPs.
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).
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.
微粒（MPs）是从活化或受损细胞释放的亚微米大小的脱落膜泡，可通过流式细胞术检测到。MP水平已被用作生物标志物，以评估病理状态患者的细胞损伤或活化情况。
我们试图比较对照组以及无鼻息肉慢性鼻-鼻窦炎（CRSsNP）、有鼻息肉慢性鼻-鼻窦炎（CRSwNP）和阿司匹林加重性呼吸疾病（AERD）患者的鼻灌洗液（NLFs）中的MP类型和水平。
我们收集了CRSsNP患者（n = 33）、CRSwNP患者（n = 45）、AERD患者（n = 31）和对照组（n = 24）受试者的NLFs。使用标准化流式细胞术方法对以下MP类型进行表征：内皮微粒、上皮微粒（上皮细胞粘附分子EpCAM微粒、E-钙粘蛋白(+)微粒）、血小板微粒（CD31(+)CD41(+)微粒）、嗜酸性粒细胞微粒（含表皮生长因子样模块的粘蛋白样激素受体样1EMR1微粒）、肥大细胞微粒（高亲和力IgE受体FcεRIc-kit(+)微粒）和嗜碱性粒细胞微粒（CD203c(+)c-kit(-)微粒）。通过嗜碱性粒细胞微粒上CD203c的平均荧光强度评估嗜碱性粒细胞活化情况。
与CRSsNP患者（2.3倍；P <.02）、CRSwNP患者（2.3倍；P <.03）和AERD患者（7.4倍；P <.0001）的NLFs相比，对照组NLFs中活化的肥大细胞微粒（CD137(+)FcεRI(+)c-kit(+)微粒）显著增加。仅AERD患者的血小板微粒（3.5倍；P <.01）和嗜碱性粒细胞微粒（2.5倍；P <.05）增加。CRSwNP患者（P <.002）和AERD患者（P <.0001）的微粒上CD203c的平均荧光强度增加，但CRSsNP患者未增加。CRSwNP患者的EpCAM(+)微粒与对照组无差异（P = 0.91），且低于CRSsNP患者（P <.02）和AERD患者（P <.002）。
基于释放的微粒，AERD患者的肥大细胞、血小板和嗜碱性粒细胞的活化程度高于CRS患者。CRSwNP患者的上皮损伤低于CRSsNP患者和AERD患者。MP分析可能有助于识别CRS的表型，并将AERD与CRSwNP区分开来。
