An association between MMP-9 and impaired T cell migration in ethanol-fed BALB/c mice infected with respiratory syncytial virus-2A.
An association between MMP-9 and impaired T cell migration in ethanol-fed BALB/c mice infected with respiratory syncytial virus-2A.
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MMP-9 与感染呼吸道合胞病毒 2A 的乙醇喂养 BALB/c 小鼠中 T 细胞迁移受损之间的关联。
DOI：
10.1016/j.alcohol.2018.09.009
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Wyatt,ToddA
中科院分区：
文献类型：
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作者：
Warren,KristiJ;Poole,JillA;Sweeter,JeneaM;DeVasure,JaneM;Wyatt,ToddA
基质金属蛋白酶对气道基质结构和创伤愈合非常重要。这些酶也与许多气道疾病有关。以前，慢性乙醇消耗被证明会延长呼吸道合胞病毒（RSV）感染小鼠的炎症和延迟病毒清除。我们假设酒精通过破坏肺中免疫细胞的趋化性来改变抗病毒免疫。随机选择BALB/c小鼠，在感染RSV-2A之前，自由饮用18%酒精8周。流式细胞术检测支气管肺泡灌洗液（BAL）细胞数，Western blot或ELISA检测趋化因子。采用聚合酶链反应（PCR）法测定小鼠肺组织和支气管肺泡灌洗液（BAL）中MMP-9的水平。在RSV感染后4天，从水喂养的、未感染的对照小鼠（CTRL）;酒精喂养的、未感染的（ETOH）;水喂养的、RSV感染的（RSV）;或乙醇喂养的、RSV感染的（ETOH-RSV）的脾脏获得T细胞。将T细胞置于其中用和不用活化的MMP-9处理趋化因子的迁移系统中。在ETOH-RSV小鼠中，RSV感染后4天，BAL中淋巴细胞募集显著减少，而与RSV相比，在所有实验时间点，该组中趋化因子水平最高（p< 0.05）。与RSV相比，在ETOH-RSV小鼠中检测到高水平的MMP-9 mRNA和蛋白。使用CCL 2和CXCL 10的体外迁移，任何治疗组之间的T细胞迁移均未受损，但当用活化的MMP-9治疗CCL 2和CXCL 10时，显著更少的T细胞迁移穿过胶原包被的5 μm膜（p< 0.05）。免疫细胞募集对于病毒清除是必要的。我们表明，免疫细胞减少在肺ETOH-RSV小鼠。与细胞募集减少相反，ETOH-RSV小鼠肺中的关键炎性趋化因子升高。这些蛋白质可能在肺中被MMP-9过早降解，导致免疫缺陷和病毒清除减少。
Matrix metalloproteinases are important for proper airway matrix structure and wound healing. These enzymes are also implicated in many airway diseases. Previously, chronic ethanol consumption was shown to prolong inflammation and delay viral clearance in respiratory syncytial virus (RSV)-infected mice. We hypothesize that alcohol alters anti-viral immunity by disrupting immune cell chemotaxis in the lung. BALB/c mice were randomly selected to consume 18% alcoholad libitumfor 8 weeks prior to infection with RSV-2A. Bronchoalveolar lavage (BAL) cell populations were measured by flow cytometry, and chemokines were detected by Western blot or ELISA. MMP-9 levels were determined by polymerase chain reaction (PCR) in mouse lungs and in BAL fluid by ELISA. T cells were acquired from the spleens of water-fed, non-infected control mice (CTRL); alcohol-fed, non-infected (ETOH); water-fed, RSV-infected (RSV); or ethanol-fed, RSV-infected (ETOH-RSV) 4 days after RSV infection. T cells were placed in a transmigration system where chemokines had been treated with and without activated MMP-9. Lymphocyte recruitment was significantly reduced in the BAL 4 days after RSV infection in ETOH-RSV mice, whereas chemokine levels were the highest in this group at all experimental time points examined in comparison to RSV (p< 0.05). MMP-9 mRNA and protein were detected at high levels in ETOH-RSV mice compared to RSV. Usingex vivotransmigration to CCL2 and CXCL10, T cell migration was not impaired between any of the treatment groups, yet when CCL2 and CXCL10 were treated with activated MMP-9, significantly fewer T cells migrated across collagen-coated 5-μm membranes (p< 0.05). Immune cell recruitment is necessary for viral clearance. We show that immune cells are decreased in the lungs of ETOH-RSV mice. In contrast to decreased cell recruitment, key inflammatory chemokines were elevated in the lungs of ETOH-RSV mice. These proteins may be prematurely degraded by MMP-9 in the lung, leading to defective immunity and reduced viral clearance.