(1. Department of Rheumatology and Immunology, 2. Department of Nutrition, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing Jiangsu 210008, China)
Abstract：Objective： To investigate the effect of mesenchymal stem cells (MSC) transplantation on pristane induced pulmonary alveolar hemorrhage in lupus mice and explore the possible mechanism. Methods： Twenty female C57BL/6 (B6) mice at 10 weeks of age were injected with 0.5 mL pristane intraperitoneally and 3 control B6 mice were injected with the same volume of PBS. After one week, mice injected with pristane were randomly divided into two groups and intravenously injected with 1×106 human umbilical cord-derived MSCs or PBS, respectively. After another week of observation, the survival rate and body weight of the two groups were recorded and all mice were sacrificed. The appearance of the lungs was observed and hematoxylin and eosin (HE) staining was performed to assess the severity of pulmonary hemorrhage. Lung single-cell suspensions were prepared by enzymatic digestion. CD4+ and CD8+ T lymphocytes, CD19+ B lymphocytes, CD11b+Gr1+ neutrophils, F4/80+ macrophages and CD206+ macrophages in lungs were detected by flow cytometry. Results： The survival rate of mice in the MSC group was higher than that of the PBS group, but the difference was not statistically significant (P=0.07), and the average body weight in MSC mice was significantly increased (P<0.01) than that in PBS group. The incidences of complete diffuse alveolar hemorrhage and partial diffuse alveolar hemorrhage in the MSC group were lower than that in the PBS group. Compared with the PBS mice, the total number of lung cells in the MSC group was significantly reduced (P<0.01) than that in the PBS group. The number of lung CD4+ T cells in the MSC group showed a decreased tendency, while the numbers of CD8+ T cells and CD19+ B cells were significantly decreased (P<0.05) in the MSC group than that in the PBS group. The absolute numbers of CD11b+Gr1+ neutrophils and F4/80+ macrophages in lungs of MSC treated mice were also markedly reduced (P<0.01 and P<0.05). In addition, the percentage of CD206+ anti-inflammatory macrophages in lungs of pulmonary hemorrhage mice was significantly reduced (P<0.01), while the percentage of CD206+ anti-inflammatory macrophages was significantly increased by MSC transplantation (P<0.01). Conclusion： MSC transplantation can significantly reduce the incidence of pulmonary hemorrhage in lupus-prone mice, which may attributed to the regulation of lung immune cells and the induction of CD206 anti-inflammatory macrophages by MSCs.
［Key words］mesenchymal stem cell; systemic lupus erythematosus; alveolar hemorrhage; macrophage; CD206
