CD19 Regulates the Development of Bleomycin-Induced Pulmonary Fibrosis in a Mouse Model
CD19 Regulates the Development of Bleomycin-Induced Pulmonary Fibrosis in a Mouse Model
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DOI：
10.1002/art.23995
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发表时间：
2008-11-01
影响因子：
--
通讯作者：
Sato, Shinichi
中科院分区：
文献类型：
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作者：
Komura, Kazubiro;Yanaba, Koichi;Sato, Shinichi
目标。CD19和B淋巴细胞在肺纤维化中的作用存在争议。本研究的目的是探讨CD19在肺纤维化发生发展中的作用。缺乏或过度表达B细胞表面分子CD19的小鼠被用于博莱霉素诱导的肺纤维化模型。CD19被认为是B细胞激活的正向调节因子。气管内注射博莱霉素10天或16天后，取小鼠肺切片进行组织学观察。灌胃7d后，采用血细胞计数法和细胞计数法检测支气管肺泡灌洗液(BALF)中白细胞总数和B细胞数。博莱霉素也被注射到选择素缺陷或细胞间黏附分子1缺陷的小鼠品系中。采用流式细胞术检测B细胞表面CXCR3的表达水平。CD19缺乏可显著降低BALF对博莱霉素攻击的敏感性，而CD19过表达在第10天仍可加重纤维化程度。此外，BALF中B细胞的存活率和数量也与CD19的表达水平相关。BALF中B细胞的聚集依赖于CD19水平，而与选择素或细胞间黏附分子1的水平无关。此外，CXCR3在BALF B细胞中表达上调，而在循环B细胞上表达很少。此外，CD19信号促进了B细胞CXCR3在体外刺激下的上调。这些结果提示CD19信号通过控制B细胞对肺组织的侵袭而参与肺纤维化的发生，这可能与CXCR3上调有关。
Objective. The contribution of CD19 and B lymphocytes to pulmonary fibrosis is controversial. The aim of this study was to address the role of CD19 during the development of pulmonary fibrosis.Methods. Mice lacking or overexpressing the B cell surface molecule CD19, which is known as a positive regulator of B cell activation, were used in a model of bleomycin-induced pulmonary fibrosis. Ten or sixteen days after intratracheal injection of bleomycin, lung sections from mice were evaluated by histologic analysis. Seven days after instillation, the total leukocyte count and the number of B cells in bronchoalveolar lavage fluid (BALF) were determined, using a hemocytometer and now cytometry. Bleomycin was also administered into selectin-deficient or intercellular adhesion molecule 1-deficient mouse strains. The level of CXCR3 expression on B cells was determined by flow cytometry.Results. CD19 deficiency significantly reduced susceptibility to intratracheal bleomycin challenge on day 16, while CD19 overexpression augmented fibrosis even on day 10. Furthermore, the survival rate and number of B cells in BALF also correlated with CD19 expression levels. The accumulation of B cells in BALF was dependent on CD19 levels, whereas there was no association with the levels of selectins or intercellular adhesion molecule 1. Additionally, CXCR3 was up-regulated in BALF B cells, while it was rarely expressed on circulating B cells. Furthermore, CD19 signaling facilitated B cell CXCR3 up-regulation in response to stimulation in vitro.Conclusion. These results suggest that CD19 signaling is associated with the development of pulmonary fibrosis by controlling B cell infiltration into lung tissue, which may be associated with CXCR3 up-regulation.