Decreased asbestos-induced lung inflammation and fibrosis after radiation and bone marrow transplant.
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.
Levis
Jamie
J
Pulmonary and Critical Care, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Loi
Roberto
R
Butnor
Kelly J
KJ
Vacek
Pamela
P
Steele
Chad
C
Mossman
Brooke T
BT
Weiss
Daniel J
DJ
D000818:Animals; D001194:Asbestos / Q000633:toxicity*; D001195:Asbestosis / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D018183:Transplantation Chimera / Q000378:metabolism*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D016207:Cytokines; D018836:Inflammation Mediators; D001194:Asbestos