BM-derived cells restore expression of peroxiredoxin V in the airways following acute naphthalene injury in mice.
BACKGROUND
Naphthalene-induced respiratory tract toxicity in mice is characterized by specific and rapid loss of the Clara cell population, which is restored only after several days. The sources of restoration of this cell population remain unclear. We investigated whether BM-derived cells participated in the process of epithelial restoration following naphthalene toxicity compared with bacterial infection. We further investigated the role of BM-derived cells in restoration of expression of peroxiredoxin V (PRXV), one of the major proteins of antioxidant defense, specifically expressed in the bronchial epithelium.


METHODS
We transplanted GFP-tagged BM cells into 5 Gy-irradiated C57BL/6 recipients. Following 1 month of recovery, experimental animals were subjected to 250 mg/kg naphthalene i.p. An additional group of animals received intratracheal instillation of Escherichia coli to induce acute bacterial inflammation. Animals were killed at 1-12 days after naphthalene and analyzed immunohistochemically.


RESULTS
Recipients' cells of bronchial epithelium demonstrated significantly reduced levels of PRXV expression following naphthalene. In animals with acute bacterial inflammation, PRXV levels were not reduced in epithelium and participation of BM-derived cells in epithelial restoration was minimal. Following naphthalene, GFP(+) cells were present in large numbers in lung parenchyma and epithelium of conducting airways starting at 1 day following injury. GFP(+) progeny of BM cells was the major source of PRXV in the epithelium.


CONCLUSIONS
These data suggest that BM-derived cells may provide a source of antioxidant protection of airways by expression of PRXV in a model of acute epithelial respiratory tract toxicity.
Serikov
V B
VB
Children's Hospital Oakland Research Institute, 5700 M. L. King Jr Way, California 94609, USA.
Popov
B V
BV
Kropotov
A V
AV
Tomilin
N V
NV
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048168:Escherichia coli K12; D005260:Female; D049452:Green Fluorescent Proteins; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009281:Naphthalenes; D010544:Peroxidases / Q000096:biosynthesis / Q000378:metabolism*; D054464:Peroxiredoxins; D013997:Time Factors; D014916:Whole-Body Irradiation
D009281:Naphthalenes; D049452:Green Fluorescent Proteins; C031721:naphthalene; D010544:Peroxidases; D054464:Peroxiredoxins