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.
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