title: [Effect of CsA bleomycin-induced interstitial pulmonary disease in mice].
abstract: OBJECTIVE
  To observe the therapeutic effect of cyclosporine A (CsA) on bleomycin (BLM) induced pulmonary fibrosis and to investigate its mechanism.
  
  
  METHODS
  One hundred and twenty C57BL/6 female mice were divided randomly into five groups:  BLM model group,  control saline group,  CsA30 mg treatment group,  CsA50 mg treatment group and control treatment group. Treatment groups and model groups were administrated BLM intratracheally to induce interstitial pulmonary disease model,  with control saline group administrated with equal volume of normal saline instead. Mice in treatment groups were intraperitoneal injected with CsA,  while control treatment group were injected with equal volume of normal saline instead. On the 4th,  7th and 14th day after administration,  8 mice of each group were sacrificed,  and the peripheral blood was obtained to count total leucocytes with counting chamber and quantify CD4(+); T cells,  CD14(+); monocytes and CD19(+); B cells by flow cytometry (FCM). Bronchoalveolar levage fluid was harvested for cell counting and Giemsa staining. Lung tissues were harvested for immunohistochemical staining and pathological examination.
  
  
  RESULTS
  The quantity of total leucocyte was higher in BLM model group than those in control saline group.The proportion of CD14(+); T cells and CD19(+);B cells in BLM model group were increased markedly than those in control saline group on the 4th,  7th and 14th day post BLM. With CsA treatment,  The proportion of CD14(+); T cells was lower than BLM model group at the same time point,  especially on the 4th day. The proportion of CD19(+); B cells were significantly lower than those of BLM model group at the same time point(7 d,  14 d). The total and classification of cells of BLM model group were increased markedly than those in control saline group,  and decreased obviously in the treatment groups at the same time point. Examination of lung tissues:  With the prolonged time of BLM administration,  it showed wider alveolar septum,  more collagen deposition,  as well as more infiltrating inflammatory cells which consisted of generous lymphocyte and few mononuclear macrophages than those in saline control group. With the prolonged time of CsA injection,  the interstitial pulmonary inflammation was remissive,  and there was less fibroblast infiltration and collagen deposition in pulmonary interstitium and periphery of bronchiole. Alveolar epithelial cells,  bronchiolar epithelial cells,  mononuclear macrophages,  neutrophils and lymphocytes were demonstrated to express CD147,  there was higher CD147 expression in BLM model group than those in CsA treatment groups.
  
  
  CONCLUSIONS
  CsA may heal BLM induced interstitial pulmonary disease by blocking CD147-CypA interaction,  then decreasing chemotaxis for the immunocyte,  and reducing migration of immunocytes to the lung and collagen deposition in the lung.
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ren
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Fan
authors.forename: Yan-hong
authors.initials: YH
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D051926:Basigin / Q000378:metabolism; D001761:Bleomycin / Q000009:adverse effects*; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D001761:Bleomycin; D051926:Basigin; D016572:Cyclosporine