Am. J. Respir. Cell Mol. Biol., Vol 10, No. 3, Mar 1994, 253-258.
Mesothelial cell proliferation: a nonspecific response to lung injury associated with fibrosis
IY Adamson, J Bakowska and DH Bowden
Department of Pathology, University of Manitoba, Winnipeg, Canada.
An early proliferative response of mesothelial and subpleural cells has
been reported in animals after inhalation or intratracheal (I.T.)
instillation to the lung of long asbestos fibers, which also induce
pulmonary fibrosis. To determine whether this cell proliferation is
directly related to asbestos exposure or is a nonspecific response to
injury, we examined [3H]thymidine (3HT) uptake by cells at the pleura after
exposing mice to 5 days of hyperoxia, to intravenous (I.V.) (3 mg) or I.T.
(0.15 mg) bleomycin, to I.T. (1 mg) silica, and to I.T. (0.1 mg)
crocidolite asbestos of mixed length. All exposures induced acute lung
injury, as shown by high levels of protein in lavage fluid. After
hyperoxia, the percentage of total lung cells labeled by 3HT in
autoradiographs was high for only a few days, as repair took place with no
increase in fibroblast growth and no subsequent development of fibrosis.
Particle or bleomycin exposure induced a prolonged increase in 3HT uptake
with enhanced fibroblast labeling over a 4- to 6-wk period. In each case,
labeled subpleural cells, mainly fibroblasts, increased up to 10-fold in
the first 2 to 4 wk. At the same time, 3HT uptake by mesothelial cells
ranged from 1.4 to 3% compared with almost zero in controls and in
oxygen-exposed mice after a few days upon return to air. These results
indicate that mesothelial and subpleural cell proliferation occurs after
various types of injury to the lung. The close temporal association between
3HT uptake by mesothelial cells and fibroblasts during the reparative phase
suggests that mesothelial cells may respond to the same cytokines that
trigger interstitial fibrosis.
