嗜碱性粒细胞在阿司匹林加重呼吸系统疾病发病中作用的研究
2021/04/23
摘要
背景：阿司匹林加重呼吸系统疾病(AERD)是以慢性鼻窦炎伴鼻息肉(CRSwNP)、哮喘和对环氧合酶-1(COX-1)酶抑制剂不耐受为特征的三联征。AERD发病的潜在机制尚不完全清楚，但AERD的特点是2型炎症表型增强。嗜碱性粒细胞是一种有效的2型效应细胞，但其在AERD病理生理学中的作用尚不清楚。
目的：比较AERD和CRSwNP患者的全身和局部嗜碱性粒细胞反应。
方法：从对照组、AERD和CRSwNP患者中收集鼻窦组织包括鼻下组织（IT）和/或鼻息肉（NP）和外周血。采用流式细胞仪检测嗜碱性粒细胞表面(CD45、Fc、εRI、CD203c)、活化(CD63)和胞内(2D7)标志物的表达。收集临床资料包括Lund-Mackay评分和肺功能。
结果：AERD NP中检测到的嗜碱性粒细胞(CD45+CD203c+FcεRI+CD117-)的平均数量(147±28细胞/mg组织)显著高于CRSwNP(69±20细胞/mg组织；p=0.01)。AERD患者循环嗜碱性粒细胞数显著升高(p=0.04)。NP中嗜碱性粒细胞的CD203c和CD63 MFI均显著高于血液（p<0.01）。AERD NP的嗜碱性粒细胞的颗粒含量标记物2D7的表达低于匹配的血液（p<0.01）或CRSwNP的NP（p=0.06），表明正在进行脱颗粒。嗜碱性粒细胞2D7 MFI与肺功能呈显著正相关(r=0.62，p=0.02)，与鼻窦炎症呈负相关(r=-0.56，p=0.004)。
结论：与CRSwNP相比，AERD患者NP中嗜碱粒细胞数量和持续脱颗粒的程度增加，这可能导致夸大AERD特有的疾病发病机制和严重程度。
Studies of the Role of Basophils in Aspirin Exacerbated Respiratory Disease Pathogenesis
Whitney W Stevens, Anna G Staudacher, Kathryn E Hulse, Julie A Poposki, Atsushi Kato, Roderick G Carter, Lydia A Suh, James E Norton, Julia H Huang, Anju T Peters, Leslie C Grammer, David B Conley, Stephanie Shintani-Smith, Bruce K Tan, Kevin C Welch, Robert C Kern, Robert P Schleimer
Abstract
BACKGROUND:Aspirin Exacerbated Respiratory Disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 (COX-1) enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type-2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear.
OBJECTIVE:To characterize the systemic and local basophil responses in AERD compared to CRSwNP patients.
METHODS: Sinonasal tissues including inferior turbinate (IT) and/or nasal polyps (NP) and peripheral blood were collected from controls, AERD, and CRSwNP patients. Expression of cell surface (CD45, FcεRI, CD203c), activation (CD63) and intracellular (2D7) markers associated with basophils were characterized using flow cytometry. Clinical data including Lund-Mackay scores and pulmonary function were obtained.
RESULTS: The mean number of basophils (CD45+CD203c+FcεRI+CD117-) detected in AERD NP (147±28 cells/mg tissue) was significantly elevated compared to CRSwNP (69±20 cells/mg tissue; p=0.01). The number of circulating basophils was significantly elevated in AERD (p=0.04). Basophils in NP had significantly higher CD203c and CD63 MFI compared to blood in both conditions (p<0.01). Basophils from AERD NP had lower expression of the granule content marker 2D7 than matched blood (p<0.01) or NP of CRSwNP (p=0.06), suggesting ongoing degranulation. Basophil 2D7 MFI significantly correlated with pulmonary function (r=0.62, p=0.02) and inversely correlated with sinonasal inflammation (r=-0.56, p=0.004).
CONCLUSIONS:Increased basophil numbers and extent of ongoing degranulation in NP of patients with AERD compared to CRSwNP may contribute to the exaggerated disease pathogenesis and severity unique to AERD.
背景：阿司匹林加重呼吸系统疾病(AERD)是以慢性鼻窦炎伴鼻息肉(CRSwNP)、哮喘和对环氧合酶-1(COX-1)酶抑制剂不耐受为特征的三联征。AERD发病的潜在机制尚不完全清楚，但AERD的特点是2型炎症表型增强。嗜碱性粒细胞是一种有效的2型效应细胞，但其在AERD病理生理学中的作用尚不清楚。
目的：比较AERD和CRSwNP患者的全身和局部嗜碱性粒细胞反应。
方法：从对照组、AERD和CRSwNP患者中收集鼻窦组织包括鼻下组织（IT）和/或鼻息肉（NP）和外周血。采用流式细胞仪检测嗜碱性粒细胞表面(CD45、Fc、εRI、CD203c)、活化(CD63)和胞内(2D7)标志物的表达。收集临床资料包括Lund-Mackay评分和肺功能。
结果：AERD NP中检测到的嗜碱性粒细胞(CD45+CD203c+FcεRI+CD117-)的平均数量(147±28细胞/mg组织)显著高于CRSwNP(69±20细胞/mg组织；p=0.01)。AERD患者循环嗜碱性粒细胞数显著升高(p=0.04)。NP中嗜碱性粒细胞的CD203c和CD63 MFI均显著高于血液（p<0.01）。AERD NP的嗜碱性粒细胞的颗粒含量标记物2D7的表达低于匹配的血液（p<0.01）或CRSwNP的NP（p=0.06），表明正在进行脱颗粒。嗜碱性粒细胞2D7 MFI与肺功能呈显著正相关(r=0.62，p=0.02)，与鼻窦炎症呈负相关(r=-0.56，p=0.004)。
结论：与CRSwNP相比，AERD患者NP中嗜碱粒细胞数量和持续脱颗粒的程度增加，这可能导致夸大AERD特有的疾病发病机制和严重程度。
(中日友好医院呼吸与危重症医学科 王静茹 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2021 Apr 2; S0091-6749 (21) 00546-7. doi: 10.1016/ j.jaci. 2021. 02. 045.)
(J Allergy Clin Immunol. 2021 Apr 2; S0091-6749 (21) 00546-7. doi: 10.1016/ j.jaci. 2021. 02. 045.)
Studies of the Role of Basophils in Aspirin Exacerbated Respiratory Disease Pathogenesis
Whitney W Stevens, Anna G Staudacher, Kathryn E Hulse, Julie A Poposki, Atsushi Kato, Roderick G Carter, Lydia A Suh, James E Norton, Julia H Huang, Anju T Peters, Leslie C Grammer, David B Conley, Stephanie Shintani-Smith, Bruce K Tan, Kevin C Welch, Robert C Kern, Robert P Schleimer
Abstract
BACKGROUND:Aspirin Exacerbated Respiratory Disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 (COX-1) enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type-2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear.
OBJECTIVE:To characterize the systemic and local basophil responses in AERD compared to CRSwNP patients.
METHODS: Sinonasal tissues including inferior turbinate (IT) and/or nasal polyps (NP) and peripheral blood were collected from controls, AERD, and CRSwNP patients. Expression of cell surface (CD45, FcεRI, CD203c), activation (CD63) and intracellular (2D7) markers associated with basophils were characterized using flow cytometry. Clinical data including Lund-Mackay scores and pulmonary function were obtained.
RESULTS: The mean number of basophils (CD45+CD203c+FcεRI+CD117-) detected in AERD NP (147±28 cells/mg tissue) was significantly elevated compared to CRSwNP (69±20 cells/mg tissue; p=0.01). The number of circulating basophils was significantly elevated in AERD (p=0.04). Basophils in NP had significantly higher CD203c and CD63 MFI compared to blood in both conditions (p<0.01). Basophils from AERD NP had lower expression of the granule content marker 2D7 than matched blood (p<0.01) or NP of CRSwNP (p=0.06), suggesting ongoing degranulation. Basophil 2D7 MFI significantly correlated with pulmonary function (r=0.62, p=0.02) and inversely correlated with sinonasal inflammation (r=-0.56, p=0.004).
CONCLUSIONS:Increased basophil numbers and extent of ongoing degranulation in NP of patients with AERD compared to CRSwNP may contribute to the exaggerated disease pathogenesis and severity unique to AERD.
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哮喘患者诱导痰中巨噬细胞的多样性和活化：对疾病严重程度和炎症表型的作用
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