298 ROLE OF THE SDF-1/CXCR4 AXIS IN THE PATHOGENESIS OF LUNG INJURY AND PULMONARY FIBROSIS. (1st January 2006)

• Record Type: Journal Article
• Authors: Xu, J.; Mora, A. L.; Shim, H.; Stecenko, A.; Brigham, K. L.; Rojas, M.
• Is Part Of: Journal of investigative medicine. Volume 54:Number 1(2006)
• Page Start: S309
• Page End: S309
• Publication Date: 2006-01-01
• Subjects: Clinical medicine -- Periodicals; Medicine -- Research -- Periodicals; Medicine; Research -- United States; Clinical medicine; Medicine -- Research; Periodicals; 616.075
• DOI: 10.2310/6650.2005.X0008.297
• Languages: English
• ISSNs: 1081-5589

Abstract

Abstract : Recent studies demonstrated that stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 participate in recruiting stem cells from bone marrow (BM). Lung fibrogenesis may result from stem cells that home to the lung and assume a fibroblast phenotype. To determine the involvement of the SDF-1/CXCR4 axis in pulmonary fibrosis, we employed a mouse pulmonary fibrosis model resulting from intratracheal instillation of bleomycin. After bleomycin treatment, SDF-1 expression in the lung and serum SDF-1 levels increased significantly with a maximum peak at day 3 (p < .05). Immunohistochemical studies revealed that macrophages and neutrophils in the lung contributed to SDF-1 production. Bleomycin treatment also elevated BM MMP-9 activity with a peak from days 3-7, which is in parallel with serum SDF-1 levels, while CXCR4 elevation occurred at delayed time points. After treatment with bleomycin, approximately 40% of total BM stem cells were revealed as CXCR4 positive. Both SDF-1 and lung lysates from bleomycin-treated mice induced BM stem cell migration in vitro, which was blocked by CXCR4 antagonist TN14003. Treatment of bleomycin-exposed mice with TN14003 significantly attenuated lung fibrosis. SDF-1 and CXCR4 positive cells were also abundant in lungs from patients with idiopathic pulmonary fibrosis.