哮喘联盟

   摘要
   心血管疾病（CVD）是慢性阻塞性肺病（COPD）常见的合并症。尽管COPD机制尚不完全明确，但吸烟与肺功能下降相关。因此，本研究在于探究水溶性烟草提取物（CSE）诱导内皮功能异常与白细胞初始黏附CXCL16/CXCR6轴之间的潜在关系，同步研究其对于COPD相关全身炎症的影响。研究中，我们采用不同的实验方法，包括RNA沉默和流式细胞学分析，动态流动室技术以及曝露于烟草（CS）活体组织显微镜检查。CSE诱导动脉CXCL16表达导致血小板-白细胞和单核细胞粘附性增加。CSE诱导CXCL16表达是Nox5表达和进一步RhoA/p38 MAPK/NF-κB表达的独立影响因素。流式细胞学分析提示与年龄匹配的对照组相比，COPD患者增加表达CXCL16和CXCR6的激活循环血小板数量（PAC-1+ 和P-选择素+）。与既往吸烟者相比，吸烟COPD组患者表达CXCR6+血小板更多。这与COPD患者循环CXCR6+血小板-白细胞聚合体增加符合。循环CXCR6表达血小板和单核细胞增加导致许血小板-白细胞和白细胞黏附CSE刺激动脉内皮能力增加，而这种差异显著高于年龄匹配组，并是部分依赖CXCL16上调。此外，CS暴露刺激CXCL16依赖的白细胞-微小动脉黏附，而在无功能性CXCR6受体动物中期表达显著下降。总之，本研究首次证实COPD患者CXCR6表达循环血小板和单核细胞可以作为全身炎症的标志物，并可以与CVD发展有关。因此，CXCL16/CXCR6轴阻断有望作为降低COPD患者CVD风险一种新的治疗方法。
 

上海交通大学医学院附属瑞金医院呼吸与危重症医学科 周剑平 万欢英 摘译）
（Potential Consequences in Chronic Obstructive Pulmonary Disease.Front Immunol. 2017 Dec 13;8:1766.）

Cigarette Smoke Increases Endothelial CXCL16-Leukocyte CXCR6 Adhesion In Vitro and In Vivo.
 

Marques P.

Abstract
Cardiovascular disease (CVD) is a major comorbidity in chronic obstructive pulmonary disease (COPD). Although the mechanism of its development remains largely unknown, it appears to be associated with cigarette consumption and reduced lung function. Therefore, the aim of this study was to investigate the potential link between water-soluble cigarette smoke extract (CSE)-induced endothelial dysfunction and the function of CXCL16/CXCR6 axis on the initial attachment of leukocytes, in addition to its possible impact on COPD-associated systemic inflammation. To do this, we employed several experimental approaches, including RNA silencing and flow cytometry analysis, the dynamic flow chamber technique, and intravital microscopy in the cremasteric arterioles of animals exposed to cigarette smoke (CS). CSE-induced arterial CXCL16 expression, leading to increased platelet-leukocyte and mononuclear cell adhesiveness. CSE-induced CXCL16 expression was dependent on Nox5 expression and subsequent RhoA/p38 MAPK/NF-κB activation. Flow cytometry analysis revealed that COPD patients presented greater numbers of activated circulating platelets (PAC-1+ and P-selectin+) expressing CXCL16 and CXCR6 as compared with age-matched controls, with a higher number of CXCR6+-platelets in the smoking COPD group than in ex-smokers. This correlated with enhanced circulating CXCR6+-platelet-leukocyte aggregates in COPD patients. The increase in circulating numbers of CXCR6-expressing platelets and mononuclear cells resulted in enhanced platelet-leukocyte and leukocyte adhesiveness to CSE-stimulated arterial endothelium, which was greater than that found in age-matched controls and was partly dependent on endothelial CXCL16 upregulation. Furthermore, CS exposure provoked CXCL16-dependent leukocyte-arteriolar adhesion in cremasteric arterioles, which was significantly reduced in animals with a nonfunctional CXCR6 receptor. In conclusion, we provide the first evidence that increased numbers of CXCR6-expressing circulating platelets and mononuclear leukocytes from patients with COPD might be a marker of systemic inflammation with potential consequences in CVD development. Accordingly, CXCL16/CXCR6 axis blockade might constitute a new therapeutic approach for decreasing the risk of CVD in COPD patients.