组胺释放因子在严重哮喘和鼻病毒相关性哮喘加重中的作用
2023/06/25
摘要
背景: 组胺释放因子(HRF)与过敏性疾病有相关性，我们之前在小鼠哮喘模型中已表明了其致病作用。
目的：为了研究HRF功能在哮喘和病毒引起的哮喘加重中的关系，对三个独立的人类样本(哮喘患者的血清样本、鼻病毒(RV)感染者的鼻冲洗液样本和RV引起的哮喘加重患者的血清样本)和一个小鼠样本进行数据分析。
方法: 采用酶联免疫吸附试验(ELISA)对轻/中度(MA)或重度哮喘(SA)患者和健康对照组(HC)等各组血清样本中的总IgE、HRF反应性IgE/ IgGs及HRF进行定量分析。采用蛋白质印迹法分析了鼻病毒感染的BEAS-2B人支气管上皮细胞培养基中HRF的分泌情况和鼻病毒感染实验对象的鼻洗液中HRF的分泌情况。同时量化分析了哮喘加重患者的纵向血清样本中HRF反应性IgE/IgG水平。
结果: SA组患者的HRF反应性 IgE和总IgE水平均高于HC组患者，而哮喘患者的HRF反应性 IgGs(和IgG1)水平低于HC组患者。对比下可看出，HRF反应性 IgE哮喘患者在抗IgE刺激支气管肺泡灌洗(BAL)细胞时，有释放更多胰蛋白酶和前列腺素D的倾向。RV感染诱导BEAS-2B细胞分泌HRF，在鼻内RV感染者的洗鼻液中可检测到HRF受诱发后分泌增加。哮喘患者在与RV感染相关的哮喘加重时的HRF反应性IgE水平高于缓解后的水平。这种现象未见于无病毒感染的哮喘加重。
结论: 重症哮喘患者会有更高的HRF相关性IgE水平。RV感染在体内和体外条件下均可诱增呼吸道上皮细胞分泌HRF。上述结果均能表明HRF在重症哮喘和RV诱导的哮喘加重中发挥一定作用。
Histamine-releasing factor in severe asthma and rhinovirus-associated asthma exacerbation.
Kawakami Y, Takazawa I, Fajt ML
Abstrast
Background: Histamine-releasing factor (HRF) is implicated in allergic diseases. We previously showed its pathogenic role in murine models of asthma.
Objective: To present data analysis from three separate human samples (sera samples from asthmatic patients, nasal washings from rhinovirus (RV) infected individuals and sera samples from patients with RV-induced asthma exacerbation) and one mouse sample in order to investigate correlates of HRF function in asthma and virus-induced asthma exacerbations.
Methods: Total IgE and HRF-reactive IgE/IgGs as well as HRF in sera from patients with mild/moderate (MA) or severe asthma (SA) and healthy controls (HC) were quantified by enzyme-linked immunosorbent assay (ELISA). HRF secretion in culture media from RV-infected BEAS-2B human bronchial epithelial cells and in nasal washings from experimentally RV-infected subjects was analyzed by western blotting. HRF-reactive IgE/IgG levels in longitudinal serum samples from patients with asthma exacerbations were also quantified.
Results: HRF-reactive IgE and total IgE were higher in SA than in HC, whereas HRF-reactive IgGs (and IgG1) were lower in asthmatics vs. HC. In comparison to HRF-reactive IgE asthmatics, HRF-reactive IgE asthmatics had tendency to release more tryptase and prostaglandin D upon anti-IgE stimulation of bronchoalveolar lavage (BAL) cells. RV infection induced HRF secretion from BEAS-2B cells, and intranasal RV infection of human subjects induced increased HRF secretion in nasal washes. Asthmatic patients had higher levels of HRF-reactive IgE at the time of asthma exacerbations associated with RV infection, compared with those after the resolution. This phenomenon was not seen in asthma exacerbations without viral infections.
Conclusions: HRF-reactive IgE is higher in severe asthmatics. RV infection induces HRF secretion from respiratory epithelial cells both in vitro and in vivo. These results suggest the role of HRF in asthma severity and RV-induced asthma exacerbation.
背景: 组胺释放因子(HRF)与过敏性疾病有相关性，我们之前在小鼠哮喘模型中已表明了其致病作用。
目的：为了研究HRF功能在哮喘和病毒引起的哮喘加重中的关系，对三个独立的人类样本(哮喘患者的血清样本、鼻病毒(RV)感染者的鼻冲洗液样本和RV引起的哮喘加重患者的血清样本)和一个小鼠样本进行数据分析。
方法: 采用酶联免疫吸附试验(ELISA)对轻/中度(MA)或重度哮喘(SA)患者和健康对照组(HC)等各组血清样本中的总IgE、HRF反应性IgE/ IgGs及HRF进行定量分析。采用蛋白质印迹法分析了鼻病毒感染的BEAS-2B人支气管上皮细胞培养基中HRF的分泌情况和鼻病毒感染实验对象的鼻洗液中HRF的分泌情况。同时量化分析了哮喘加重患者的纵向血清样本中HRF反应性IgE/IgG水平。
结果: SA组患者的HRF反应性 IgE和总IgE水平均高于HC组患者，而哮喘患者的HRF反应性 IgGs(和IgG1)水平低于HC组患者。对比下可看出，HRF反应性 IgE哮喘患者在抗IgE刺激支气管肺泡灌洗(BAL)细胞时，有释放更多胰蛋白酶和前列腺素D的倾向。RV感染诱导BEAS-2B细胞分泌HRF，在鼻内RV感染者的洗鼻液中可检测到HRF受诱发后分泌增加。哮喘患者在与RV感染相关的哮喘加重时的HRF反应性IgE水平高于缓解后的水平。这种现象未见于无病毒感染的哮喘加重。
结论: 重症哮喘患者会有更高的HRF相关性IgE水平。RV感染在体内和体外条件下均可诱增呼吸道上皮细胞分泌HRF。上述结果均能表明HRF在重症哮喘和RV诱导的哮喘加重中发挥一定作用。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2023 Jun 08; doi: 10.1016/j.jaci.2023.04.021. IF: 10.228)
(J Allergy Clin Immunol. 2023 Jun 08; doi: 10.1016/j.jaci.2023.04.021. IF: 10.228)
Histamine-releasing factor in severe asthma and rhinovirus-associated asthma exacerbation.
Kawakami Y, Takazawa I, Fajt ML
Abstrast
Background: Histamine-releasing factor (HRF) is implicated in allergic diseases. We previously showed its pathogenic role in murine models of asthma.
Objective: To present data analysis from three separate human samples (sera samples from asthmatic patients, nasal washings from rhinovirus (RV) infected individuals and sera samples from patients with RV-induced asthma exacerbation) and one mouse sample in order to investigate correlates of HRF function in asthma and virus-induced asthma exacerbations.
Methods: Total IgE and HRF-reactive IgE/IgGs as well as HRF in sera from patients with mild/moderate (MA) or severe asthma (SA) and healthy controls (HC) were quantified by enzyme-linked immunosorbent assay (ELISA). HRF secretion in culture media from RV-infected BEAS-2B human bronchial epithelial cells and in nasal washings from experimentally RV-infected subjects was analyzed by western blotting. HRF-reactive IgE/IgG levels in longitudinal serum samples from patients with asthma exacerbations were also quantified.
Results: HRF-reactive IgE and total IgE were higher in SA than in HC, whereas HRF-reactive IgGs (and IgG1) were lower in asthmatics vs. HC. In comparison to HRF-reactive IgE asthmatics, HRF-reactive IgE asthmatics had tendency to release more tryptase and prostaglandin D upon anti-IgE stimulation of bronchoalveolar lavage (BAL) cells. RV infection induced HRF secretion from BEAS-2B cells, and intranasal RV infection of human subjects induced increased HRF secretion in nasal washes. Asthmatic patients had higher levels of HRF-reactive IgE at the time of asthma exacerbations associated with RV infection, compared with those after the resolution. This phenomenon was not seen in asthma exacerbations without viral infections.
Conclusions: HRF-reactive IgE is higher in severe asthmatics. RV infection induces HRF secretion from respiratory epithelial cells both in vitro and in vivo. These results suggest the role of HRF in asthma severity and RV-induced asthma exacerbation.
上一篇：
人类遗传学影响下的与吸入皮质类固醇治疗后哮喘恶化相关的微生物组组分研究
下一篇：
中性粒细胞外陷阱的产生和CCL4L2的表达对哮喘皮质类固醇反应的影响
