Komura Kazuhiro, Yanaba Koichi, Horikawa Mayuka, Ogawa Fumihide, Fujimoto Manabu, Tedder Thomas F, Sato Shinichi
Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Arthritis Rheum. 2008 Nov;58(11):3574-84. doi: 10.1002/art.23995.
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.
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 flow 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.
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.
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.
CD19和B淋巴细胞对肺纤维化的作用存在争议。本研究旨在探讨CD19在肺纤维化发生发展过程中的作用。
利用缺乏或过表达B细胞表面分子CD19（已知为B细胞活化的正调节因子）的小鼠，建立博来霉素诱导的肺纤维化模型。气管内注射博来霉素10或16天后，通过组织学分析评估小鼠的肺组织切片。滴注7天后，使用血细胞计数器和流式细胞术测定支气管肺泡灌洗液（BALF）中的总白细胞计数和B细胞数量。还将博来霉素注射到缺乏选择素或细胞间黏附分子1的小鼠品系中。通过流式细胞术测定B细胞上CXCR3的表达水平。
CD19缺陷显著降低了第16天对气管内博来霉素攻击的易感性，而CD19过表达即使在第10天也加剧了纤维化。此外，BALF中的存活率和B细胞数量也与CD19表达水平相关。BALF中B细胞的积累依赖于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细胞中上调，而在循环B细胞中很少表达。此外，CD19信号在体外刺激下促进B细胞CXCR3上调。
这些结果表明，CD19信号通过控制B细胞向肺组织的浸润与肺纤维化的发生发展相关，这可能与CXCR3上调有关。
