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Published ahead of print on August 2, 2007, doi:10.1165/rcmb.2007-0249OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 38, pp. 16-25, 2008
© 2008 American Thoracic Society
DOI: 10.1165/rcmb.2007-0249OC

Decreased Asbestos-Induced Lung Inflammation and Fibrosis after Radiation and Bone Marrow Transplant

Jamie Levis1, Roberto Loi2, Kelly J. Butnor1, Pamela Vacek3, Chad Steele4, Brooke T. Mossman1 and Daniel J. Weiss2

Departments of 1 Pathology, 2 Medicine, and 3 Biostatistics, University of Vermont College of Medicine, Burlington, Vermont; and 4 Department of Pediatrics, University of Pittsburgh College of Medicine, Pittsburgh, Pennsylvania

Correspondence and requests for reprints should be addressed to Daniel J. Weiss, M.D., Ph.D., Pulmonary and Critical Care, University of Vermont College of Medicine, Burlington, VT 05405. E-mail: dweiss{at}uvm.edu

The effect of lung irradiation on subsequent inflammatory or fibrotic lung injuries remains poorly understood. We postulated that irradiation and bone marrow transplantation might impact the development and progression of lung remodeling resulting from asbestos inhalation. Our objective was to determine whether irradiation and bone marrow transplantation affected inflammation and fibrosis associated with inhaled asbestos exposure. Inflammation, cytokine production, and fibrosis were assessed in lungs of naïve and sex-mismatched chimeric mice exposed to asbestos for 3, 9, or 40 days. Potential engraftment of donor-derived cells in recipient lungs was examined by fluorescence in situ hybridization and immunohistochemistry. Compared with asbestos-exposed naïve (nonchimeric) mice, chimeric mice exposed to asbestos for 3, 9, or 40 days demonstrated significant abrogation of acute increases in asbestos-associated inflammatory mediators and fibrosis. Donor-derived cells trafficked to lung but did not significantly engraft as phenotypic lung cells. Irradiation and bone marrow transplantation alters inflammatory and fibrotic responses to asbestos, likely through modulation of soluble inflammatory mediators.

Key Words: irradiation • asbestosis • stem cell • inflammation • fibrosis


CLINICAL RELEVANCE

This article presents novel data that asbestos-induced lung inflammation and fibrosis are modulated following myeloablation and bone marrow transplantation.

 



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D. J. Weiss, J. K. Kolls, L. A. Ortiz, A. Panoskaltsis-Mortari, and D. J. Prockop
Stem Cells and Cell Therapies in Lung Biology and Lung Diseases
Proceedings of the ATS, July 15, 2008; 5(5): 637 - 667.
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Copyright © 2008 American Thoracic Society.