Engraftment of bone marrow progenitor cells in a rat model of asbestos-induced pulmonary fibrosis.
BACKGROUND
Bone marrow-derived cells have been shown to engraft during lung fibrosis. However, it is not known if similar cells engraft consequent to inhalation of asbestos fibers that cause pulmonary fibrosis, or if the cells proliferate and differentiate at sites of injury.


OBJECTIVE
We examined whether bone marrow-derived cells participate in the pulmonary fibrosis that is produced by exposure to chrysotile asbestos fibers.


METHODS
Adult female rats were lethally irradiated and rescued by bone marrow transplant from male transgenic rats ubiquitously expressing green fluorescent protein (GFP). Three weeks later, the rats were exposed to an asbestos aerosol for 5 hours on three consecutive days. Controls were bone marrow-transplanted but not exposed to asbestos.


RESULTS
One day and 2.5 weeks after exposure, significant numbers of GFP-labeled male cells had preferentially migrated to the bronchiolar-alveolar duct bifurcations, the specific anatomic site at which asbestos produces the initial fibrogenic lesions. GFP-positive cells were present at the lesions as monocytes and macrophages, fibroblasts, and myofibroblasts or smooth muscle cells. Staining with antibodies to PCNA demonstrated that some of the engrafted cells were proliferating in the lesions and along the bronchioles. Negative results for TUNEL at the lesions confirmed that both PCNA-positive endogenous pulmonary cells and bone marrow-derived cells were proliferating rather than undergoing apoptosis, necrosis, or DNA repair.


CONCLUSIONS
Bone marrow-derived cells migrated into developing fibrogenic lesions, differentiated into multiple cell types, and persisted for at least 2.5 weeks after the animals were exposed to aerosolized chrysotile asbestos fibers.
Spees
Jeffrey L
JL
Department of Medicine, Cardiovascular Research Institute, University of Vermont, 208 South Park Drive, Suite 2, Colchester, VT 05446, USA. Jeffrey.Spees@uvm.edu
Pociask
Derek A
DA
Sullivan
Deborah E
DE
Whitney
Mandolin J
MJ
Lasky
Joseph A
JA
Prockop
Darwin J
DJ
Brody
Arnold R
AR
D000818:Animals; D001195:Asbestosis / Q000473:pathology*; D001854:Bone Marrow Cells / Q000473:pathology; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D020287:In Situ Nick-End Labeling; D049408:Luminescent Agents; D008168:Lung / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D049408:Luminescent Agents; D018809:Proliferating Cell Nuclear Antigen; D049452:Green Fluorescent Proteins