title: [The circulating fibrocytes are associated with the lung inflammation and fibrosis of mice with interstitial lung disease].
abstract: OBJECTIVE
  To study the pathological process and characteristics of bleomycin (BLM)-induced interstitial lung disease (ILD) model and collagen-induced arthritis (CIA) complicated by BLM-induced ILD (CIA-ILD) model in mice and explore the correlations with circulating fibrocytes.
  
  
  METHODS
  Ninety mice were randomly divided into normal saline group (S group), BLM group (B group), CIA-BLM group (CB group), with 30 mice in each group. On the 2, 7, 14, 21 and 28 days after BLM challenge, mice of each group were sacrificed. HE staining was used to detect the degrees of acute inflammation and sirius red staining to detect lung fibrosis. Immunohistochemicstry was adopted to detect alpha-smooth muscle actin expression. The peripheral blood was obtained to count the proportion of circulating fibrocytes (CD45⁺COL1⁺) by flow cytometry. The correlations between circulating fibrocytes and pathological changes of ILD were analyzed statistically.
  
  
  RESULTS
  Both of the ILD model groups showed the dynamic process from pulmonary alveolitis to fibrosis gradually. Inflammatory lesion in the lungs of B group was the most obvious on the 7-14th day, and then there was a slow rehabilitation process on the 21th and 28th day. CB group began to present alveoli destruction and collagen deposition on the 14th day, and the inflammation was the most severe on the 28th day. Pulmonary hydroxyproline content was obviously ascended in CB group as compared with B group (P<0.05) after 14 days. An increase in the total number of circulating fibrocytes was observed in both B and CB groups. It tended to increase at first, and subsequently declined. The level of circulating fibrocytes was higher in CB group than in B group on day 14, 21 and 28 (P<0.05). The immunohistochemical results showed that there were many myofibroblasts infiltrating in CB group from the 14th day to 28th day. The number of circulating fibrocytes in peripheral blood was positively correlated with pulmonary inflammation, fibrosis degree and hydroxyproline content (r=0.847, 0.826, 0.735, P<0.01).
  
  
  CONCLUSIONS
  The pathological process of CIA-ILD animal model is more close to rheumatoid arthritis-induced ILD development. Circulating fibrocytes may be involved in the inflammation and fibrosis progression of lung.
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yalu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Mengyao
authors.initials: M
authors.lastname: Rong
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Fu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000473:pathology; D001761:Bleomycin; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D013997:Time Factors
chemical_list: D000199:Actins; D024042:Collagen Type I; D001761:Bleomycin; D017493:Leukocyte Common Antigens; D006909:Hydroxyproline