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Am J Respir Cell Mol Biol. 2007 Sep;37(3):291-9. Epub 2007 Apr 26.

Role of the SDF-1/CXCR4 axis in the pathogenesis of lung injury and fibrosis.

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1
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.

Abstract

Stromal cell-derived factor-1 (SDF-1) participates in mobilizing bone marrow-derived stem cells, via its receptor CXCR4. We studied the role of the SDF-1/CXCR4 axis in a rodent model of bleomycin-induced lung injury in C57BL/6 wild-type and matrix metalloproteinase (MMP)-9 knockout mice. After intratracheal instillation of bleomycin, SDF-1 levels in serum and bronchial alveolar lavage fluid increased. These changes were accompanied by increased numbers of CXCR4(+) cells in the lung and a decrease in a population of CXCR4(+) cells in the bone marrow that did not occur in MMP-9(-)/(-) mice. Both SDF-1 and lung lysates from bleomycin-treated mice induced migration of bone marrow-derived stem cells in vitro that was blocked by a CXCR4 antagonist, TN14003. Treatment of mice with TN14003 with bleomycin-induced lung injury significantly attenuated lung fibrosis. Lung tissue from patients with idiopathic pulmonary fibrosis had higher numbers of cells expressing both SDF-1 and CXCR4 than did normal lungs. Our data suggest that the SDF-1/CXCR4 axis is important in the complex sequence of events triggered by bleomycin exposure that eventuates in lung repair. SDF-1 participates in mobilizing bone marrow-derived stem cells, via its receptor CXCR4.

PMID:
17463394
PMCID:
PMC1994230
DOI:
10.1165/rcmb.2006-0187OC
[Indexed for MEDLINE]
Free PMC Article
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