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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access originally published online on April 9, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2009 64A(7):731-739; doi:10.1093/gerona/glp040
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Use of Senescence-Accelerated Mouse Model in Bleomycin-Induced Lung Injury Suggests That Bone Marrow–Derived Cells Can Alter the Outcome of Lung Injury in Aged Mice

Jianguo Xu1,2, Edilson T. Gonzalez1,2, Smita S. Iyer1,2, Valerie Mac1,2, Ana L. Mora1,2,3, Roy L. Sutliff1, Alana Reed1, Kenneth L. Brigham1,2,3, Patricia Kelly1,2 and Mauricio Rojas1,2,3

1 Division of Pulmonary, Allergy and Critical Care Medicine
2 Center for Translational Research in the Lung
3 McKelvey Center for Lung Transplantation, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia

Address correspondence to Mauricio Rojas, MD, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322. Email: mrojas{at}emory.edu


  Abstract

The incidence of pulmonary fibrosis increases with age. Studies from our group have implicated circulating progenitor cells, termed fibrocytes, in lung fibrosis. In this study, we investigate whether the preceding determinants of inflammation and fibrosis were augmented with aging. We compared responses to intratracheal bleomycin in senescence-accelerated prone mice (SAMP), with responses in age-matched control senescence-accelerated resistant mice (SAMR). SAMP mice demonstrated an exaggerated inflammatory response as evidenced by lung histology. Bleomycin-induced fibrosis was significantly higher in SAMP mice compared with SAMR controls. Consistent with fibrotic changes in the lung, SAMP mice expressed higher levels of transforming growth factor-β1 in the lung. Furthermore, SAMP mice showed higher numbers of fibrocytes and higher levels of stromal cell–derived factor-1 in the peripheral blood. This study provides the novel observation that apart from increases in inflammatory and fibrotic factors in response to injury, the increased mobilization of fibrocytes may be involved in age-related susceptibility to lung fibrosis.

Keywords Lung; Senescence; Bone marrow; Mice

Received: December 5, 2008; Accepted: February 25, 2009

Decision Editor: Huber R. Warner, PhD


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