Tang Francesca S M, Hansbro Philip M, Burgess Janette K, Ammit Alaina J, Baines Katherine J, Oliver Brian G
Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia Discipline of Pharmacology, Faculty of Medicine, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia.
Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia.
Thorax. 2016 Nov;71(11):1039-1049. doi: 10.1136/thoraxjnl-2015-207781. Epub 2016 Jun 10.
Rhinovirus (RV) infections are the major precipitant of asthma exacerbations. While neutrophilic lung inflammation occurs during such infections, its role remains unclear. Neutrophilic inflammation is associated with increased asthma severity and steroid refractory disease. Neutrophils are vital for controlling infections but also have immunomodulatory functions. Previously, we found that neutrophils respond to viral mimetics but not replication competent RV. We aimed to investigate if neutrophils are activated and/or modulate immune responses of monocytes during RV16 infection.
Primary human monocytes and autologous neutrophils were cocultured with or without RV16, in direct contact or separated by transwells. RV16-stimulated monocytes were also exposed to lysed neutrophils, neutrophil membrane components or soluble neutrophil intracellular components. Interleukin 6 (IL-6) and C-X-C motif (CXC)L8 mRNA and proteins were measured by quantitative PCR and ELISA at 24 hours.
RV16 induced IL-6 and CXCL8 in monocytes, but not neutrophils. RV16-induced IL-6 and CXCL8 from monocytes was reduced in the presence of live neutrophils. Transwell separation abolished the inhibitory effects. Lysed neutrophils inhibited RV16-induced IL-6 and CXCL8 from monocytes. Neutrophil intracellular components alone effectively inhibited RV16-induced monocyte-derived IL-6 and CXCL8. Neutrophil intracellular components reduced RV16-induced IL-6 and CXCL8 mRNA in monocytes.
Cell contact between monocytes and neutrophils is required, and preformed neutrophil mediator(s) are likely to be involved in the suppression of cytokine mRNA and protein production. This study demonstrates a novel regulatory function of neutrophils on RV-activated monocytes in vitro, challenging the paradigm that neutrophils are predominantly proinflammatory.
鼻病毒（RV）感染是哮喘急性加重的主要诱因。虽然在这类感染期间会发生嗜中性粒细胞性肺部炎症，但其作用仍不清楚。嗜中性粒细胞性炎症与哮喘严重程度增加和激素抵抗性疾病有关。中性粒细胞对于控制感染至关重要，但也具有免疫调节功能。此前，我们发现中性粒细胞对病毒模拟物有反应，但对具有复制能力的RV无反应。我们旨在研究在RV16感染期间中性粒细胞是否被激活和/或调节单核细胞的免疫反应。
将原代人单核细胞和自体中性粒细胞与RV16一起或不与RV16共培养，直接接触或通过Transwell小室隔开。受RV16刺激的单核细胞也暴露于裂解的中性粒细胞、中性粒细胞膜成分或可溶性中性粒细胞细胞内成分中。在24小时时通过定量PCR和ELISA测量白细胞介素6（IL-6）和C-X-C基序（CXC）L8的mRNA和蛋白。
RV16诱导单核细胞产生IL-6和CXCL8，但不诱导中性粒细胞产生。在有活的中性粒细胞存在的情况下，RV16诱导单核细胞产生的IL-6和CXCL8减少。Transwell小室隔开消除了这种抑制作用。裂解的中性粒细胞抑制RV16诱导单核细胞产生IL-6和CXCL8。单独的中性粒细胞细胞内成分有效地抑制RV16诱导的单核细胞来源的IL-6和CXCL8。中性粒细胞细胞内成分降低了RV16诱导的单核细胞中IL-6和CXCL8的mRNA。
单核细胞和中性粒细胞之间需要细胞接触，预先形成的中性粒细胞介质可能参与抑制细胞因子mRNA和蛋白的产生。本研究在体外证明了中性粒细胞对RV激活的单核细胞具有新的调节功能，挑战了中性粒细胞主要是促炎的范式。
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