Am. J. Respir. Cell Mol. Biol., Vol 16, No. 6, 06 1997, 650-656.
Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage supernatants and to lavage fluids from crocidolite-exposed rats
IY Adamson, H Prieditis and L Young
Department of Pathology, University of Manitoba, Winnipeg, Canada.
An early phase of proliferation by mesothelial cells and fibroblasts occurs
in the lung after asbestos deposition, but the source and identity of the
cytokine(s) involved is not clear. In the present study, rats received
crocidolite asbestos intratracheally and were killed at 1 and 6 wk later,
animals received tritiated thymidine 1 h before death. An increase in
inflammatory cells was found in bronchoalveolar and pleural lavage fluids
at both times, and after 6 wk the lungs showed fibrosis which was confirmed
biochemically. Asbestos fibers were found in alveolar and interstitial
macrophages but not in pleural macrophages. In autoradiographs, both
mesothelial cells and fibroblasts showed increased DNA synthesis at 1 wk,
but only fibroblast labeling was increased at 6 wk. Lavaged macrophages
from the lung (alveolar macrophages; AM) and the pleura (pleural
macrophages; PLM) were cultured and supernatants tested on rat lung
mesothelial cells and fibroblasts in vitro; concentrated lavaged fluids
were also tested. At 1 wk, macrophages secreted growth factors for both
cell types but the effect was more pronounced using lavage fluids,
particularly from the pleura. The increase in fibroblast growth was reduced
by an antibody to platelet-derived growth factor, but this had no effect on
mesothelial cells. The growth stimulation of these cells was blocked by an
antibody to keratinocyte growth factor (KGF). Using cell supernatants and
lavage fluids from rats 6 wk after asbestos, growth stimulation was only
observed in fibroblasts. The results suggest at least 2 cytokine effects in
the lung and pleural space after asbestos exposure; one responsible for
fibroblast stimulation is seen up to 6 wk later, while the other, probably
involving KGF, stimulates mesothelial cell proliferation in the early
response phase after a single exposure to crocidolite.
