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

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.

• Authors: Jianguo Xu, Ana Mora, Hyunsuk Shim, Arlene Stecenko, Kenneth L Brigham, Mauricio Rojas
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 37 Issue 3 Pg. 291-9 (Sep 2007) ISSN: 1044-1549 [Print] United States
• PMID: 17463394 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• CXCR4 protein, mouse
• Chemokine CXCL12
• Cxcl12 protein, mouse
• Peptides
• Receptors, CXCR4
• TN14003
• Bleomycin
• Matrix Metalloproteinase 9
• Mmp9 protein, mouse

Topics

• Animals
• Bleomycin (toxicity)
• Bone Marrow Cells (metabolism, pathology)
• Cell Movement (physiology)
• Chemokine CXCL12 (metabolism)
• Female
• Hematopoietic Stem Cells (metabolism, pathology)
• Humans
• In Vitro Techniques
• Lung (drug effects, metabolism)
• Lung Injury
• Matrix Metalloproteinase 9 (deficiency, genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Peptides (pharmacology)
• Pulmonary Fibrosis (etiology, metabolism, pathology)
• Receptors, CXCR4 (antagonists & inhibitors, metabolism)