Rhinovirus induction of fractalkine (CX3CL1) in airway and peripheral blood mononuclear cells in asthma.

Rhinovirus induction of fractalkine (CX3CL1) in airway and peripheral blood mononuclear cells in asthma.
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DOI:
10.1371/journal.pone.0183864
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Sykes A
Sykes A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Upton N;Jackson DJ;Nikonova AA;Hingley-Wilson S;Khaitov M;Del Rosario A;Traub S;Trujillo-Torralbo MB;Habibi M;Elkin SL;Kon OM;Edwards MR;Mallia P;Footitt J;Macintyre J;Stanciu LA;Johnston SL;Sykes A

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鼻病毒感染与大多数哮喘恶化有关。Fractalkine在过敏性哮喘中对鼻病毒感染的抗病毒(1型)和致病性(2型)反应中的作用尚不清楚。为了确定(1)是否在呼吸道细胞和外周血白细胞中产生了Fractalkine,(2)鼻病毒感染增加了Fractalkine的产生,(3)哮喘患者与非哮喘患者相比,Fractalkine的水平不同。检测非哮喘对照组(n=15)和轻度过敏性哮喘(n=15)患者的支气管肺泡灌洗(BAL)细胞和外周血单个核细胞(PBMC)中Fractalkine蛋白和mRNA水平。此外,还检测了在体鼻病毒感染前后,M1(1型)和M2(2型)巨噬细胞极化的巨噬细胞以及轻度(n=11)和中度(n=14)过敏性哮喘和非哮喘对照组(n=10)患者的BAL液中Fractalkine的蛋白水平。BAL细胞产生的Fractalkine水平明显高于PBMC。鼻病毒感染增加了非哮喘对照组的BAL细胞(P<0.01)和M1极化的巨噬细胞(P<0.05)的Fractalkine的产生,但对轻度哮喘的BAL细胞或M2极化的巨噬细胞没有影响。鼻病毒可诱导哮喘患者(P<0.001)和健康对照组(P<005)PBMC产生Fractalkine。中度哮喘受试者在活体鼻病毒感染期间诱导Fractalkine的趋势没有达到统计学意义。Fractalkine可能参与鼻病毒感染的免疫病理和抗病毒免疫反应。为了更好地了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,有必要进一步研究Fractalkine是如何在不同类型的细胞中调节的,以及包括鼻病毒感染在内的刺激的影响。
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.
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