CCL20抗体对慢性阻塞性肺疾病大鼠外周血和肺泡灌洗液中树突状细胞表面因子表达的影响

Effects of CCL20 antibody on expressions of surface factors of DCs in peripheral blood and BALF of rats with COPD

目的:研究CC亚族趋化因子配体20(CCL20)和树突状细胞(DCs)在慢性阻塞性肺疾病(COPD)发病过程中的作用及抗CCL20抗体治疗对COPD外周血和肺泡灌洗液(BALF)中DCs表面因子表达的影响。方法:选取雄性SPF级Wistar大鼠48只,随机分为正常对照组、COPD模型组和CCL20抑制组,每组16只。用烟熏及气道内滴注脂多糖(LPS)方法制备COPD大鼠模型。HE染色观察3组大鼠肺组织病理学改变。采用酶联免疫法(ELISA)检测3组大鼠BALF及外周血中CCL20的含量,流式细胞术(FCM)检测3组大鼠外周血和BALF中DCs各细胞因子(CD80、CD86、MHC-Ⅱ和OX-62)的百分比。结果:COPD组和CCL20抑制组大鼠肺组织HE染色均显示气道炎症和肺气肿表现,但后者气道炎症和肺气肿表现较前者减轻。与正常对照组比较,COPD组和CCL20抑制组大鼠外周血及BALF中CCL20含量增加(P<0.05);与COPD组比较,CCL20抑制组大鼠外周血中CCL20含量未见改变,但BALF中CCL20含量降低(P<0.05)。与正常对照组比较,COPD组大鼠外周血中CD80、CD86和OX-62百分比均升高(P<0.05);与COPD组比较,CCL20抑制组大鼠外周血中CD86和OX-62百分比均降低(P<0.05)。与正常对照组比较,COPD组及CCL20抑制组大鼠BALF中CD80和CD86百分比均升高(P<0.05);与COPD组比较,CCL20抑制组大鼠BALF中CD80百分比降低(P<0.05)。结论:CCL20参与了COPD的发病过程,CCL20抗体对该过程有一定的抑制作用。CCL20抗体可以减轻DCs在外周血中的增加和气道内的募集,从而延缓气道炎症或肺气肿的产生。

Objective To study the role of CC chemokine ligand-20（CCL20）and dendritic cells（DCs） in the pathogenesis of chronic obstructive pulmonary disease（COPD） and the influence of anti-rat CCL20 antibody treatment on the expressions of surface factors of DCs in peripheral blood and brochoalveolar lavage fluid（BALF）.Methods 48 Wistar rats were randomly divided into control group（n=16）,COPD model group（n=16） and CCL20 inhibited model group（n=16）.The rat COPD models were established via cigarette inhalation about for 4 weeks and intratracheal administration of lipopolysaccharide（LPS） solution twice totally.The patholgical changes of rat lung tissues in three groups were observed with HE staining.The CCL20 contents in peripheral blood and BALF of rats in three groups were detected with ELISA.The percentages of CD80,CD86,OX-62 and MHC-Ⅱ of DCs were analyzed by FCM.Results The HE staining results suggested that there were airway inflammation and development of emphysema of rats in COPD group and CCL20 inhibited model group,but they were reduced in latter group.compared with control group,the contents of CCL20 in BALF and peripheral blood in COPD group and CCL20 inhibited model group were significantly increased（P0.05）;compared with COPD group,the content of CCL20 in BALF of rats in CCL20 inhibited model group was decreased（P0.05）,but the content of CCL20 in peripheral blood had no change.Compared with control group,the percentages of CD80,CD86 and OX-62 in peripheral blood of rats in COPD group were increased（P0.05）;compared with COPD group,the percentages of CD80 and OX-62 of rats in CCL20 inhibited model group were decreased（P0.05）.Compared with control group,the percentages of CD80 and CD86 in BALF of rats in COPD group and CCL20 inhibited model group were increased（P0.05）;compared with COPD group,the percentage of CD80 in CCL20 inhibited model group was decreased（P0.05）.Conclusion CCL20 may be involved in the pathogenesis of COPD,anti-rat CCL20 antibody may play a inhibitory effect in this pathogenesis,it can decrease the number of DCs in the peripheral blood and the airway of COPD,and the downgulation of DCs may help to reduce the systemic inflammatory response of COPD.