Upton Nadine, Jackson David J, Nikonova Alexandra A, Hingley-Wilson Suzie, Khaitov Musa, Del Rosario Ajerico, Traub Stephanie, Trujillo-Torralbo Maria-Belen, Habibi Max, Elkin Sarah L, Kon Onn M, Edwards Michael R, Mallia Patrick, Footitt Joseph, Macintyre Jonathan, Stanciu Luminita A, Johnston Sebastian L, Sykes Annemarie
Airway Disease Infection Section, National Heart & Lung Institute, Imperial College London, London, United Kingdom.
MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
PLoS One. 2017 Aug 31;12(8):e0183864. doi: 10.1371/journal.pone.0183864. eCollection 2017.
Rhinovirus infection is associated with the majority of asthma exacerbations. The role of fractalkine in anti-viral (type 1) and pathogenic (type 2) responses to rhinovirus infection in allergic asthma is unknown. To determine whether (1) fractalkine is produced in airway cells and in peripheral blood leucocytes, (2) rhinovirus infection increases production of fractalkine and (3) levels of fractalkine differ in asthmatic compared to non-asthmatic subjects. Fractalkine protein and mRNA levels were measured in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from non-asthmatic controls (n = 15) and mild allergic asthmatic (n = 15) subjects. Protein levels of fractalkine were also measured in macrophages polarised ex vivo to give M1 (type 1) and M2 (type 2) macrophages and in BAL fluid obtained from mild (n = 11) and moderate (n = 14) allergic asthmatic and non-asthmatic control (n = 10) subjects pre and post in vivo rhinovirus infection. BAL cells produced significantly greater levels of fractalkine than PBMCs. Rhinovirus infection increased production of fractalkine by BAL cells from non-asthmatic controls (P<0.01) and in M1-polarised macrophages (P<0.05), but not in BAL cells from mild asthmatics or in M2 polarised macrophages. Rhinovirus induced fractalkine in PBMCs from asthmatic (P<0.001) and healthy control subjects (P<0.05). Trends towards induction of fractalkine in moderate asthmatic subjects during in vivo rhinovirus infection failed to reach statistical significance. Fractalkine may be involved in both immunopathological and anti-viral immune responses to rhinovirus infection. Further investigation into how fractalkine is regulated across different cell types and into the effect of stimulation including rhinovirus infection is warranted to better understand the precise role of this unique dual adhesion factor and chemokine in immune cell recruitment.
鼻病毒感染与大多数哮喘发作相关。在过敏性哮喘中，趋化因子在针对鼻病毒感染的抗病毒（1型）和致病（2型）反应中的作用尚不清楚。目的是确定：（1）气道细胞和外周血白细胞中是否产生趋化因子；（2）鼻病毒感染是否会增加趋化因子的产生；（3）哮喘患者与非哮喘患者的趋化因子水平是否存在差异。对15名非哮喘对照者和15名轻度过敏性哮喘患者的支气管肺泡灌洗（BAL）细胞和外周血单核细胞（PBMC）中的趋化因子蛋白和mRNA水平进行了检测。还对体外极化产生M1（1型）和M2（2型）巨噬细胞的巨噬细胞以及从轻度（11例）和中度（14例）过敏性哮喘患者及非哮喘对照者（10例）体内鼻病毒感染前后获得的BAL液中的趋化因子蛋白水平进行了检测。BAL细胞产生的趋化因子水平明显高于PBMC。鼻病毒感染增加了非哮喘对照者BAL细胞（P<0.01）和M1极化巨噬细胞（P<0.05）中趋化因子的产生，但在轻度哮喘患者的BAL细胞或M2极化巨噬细胞中未增加。鼻病毒可诱导哮喘患者（P<0.001）和健康对照者PBMC中趋化因子的产生（P<0.05）。体内鼻病毒感染期间中度哮喘患者趋化因子诱导的趋势未达到统计学意义。趋化因子可能参与了对鼻病毒感染的免疫病理和抗病毒免疫反应。有必要进一步研究趋化因子在不同细胞类型中的调控方式以及包括鼻病毒感染在内的刺激作用，以更好地理解这种独特的双重黏附因子和趋化因子在免疫细胞募集中的确切作用。
