Fibroblast inhibition and prostaglandin secretion by alveolar epithelial cells exposed to silica.
The possibility that the interaction of silica with the alveolar epithelium can produce factors that alter fibroblast activity in the lung is investigated. Isolated type 2 cells, which were attenuated after a few days in culture, were then exposed to doses of silica from 50 to 200 micrograms/ml for 24 hours. Silica particles were found in the epithelial cell cytoplasm without causing cell necrosis. Subsequently, serum-free supernatants of these epithelial cells were collected over 4 hours and tested on fibroblast growth and collagen production. Growth of quiescent fibroblasts was not stimulated, whereas proliferation of rapidly growing cells was inhibited by supernants of type 2 cells exposed to silica at doses of 100 micrograms/ml and above; proline incorporation into collagen was also significantly reduced. Silica exposure resulted in a 6-fold greater secretion of prostaglandin E2 by type 2 cells as shown by radioimmunoassay, and the fibroblast growth inhibition was eliminated by treating the epithelial cells with indomethacin at the time of silica exposure. These results demonstrate that, in response to silica, alveolar epithelial cells secrete a factor(s) that that inhibits fibroblast growth and collagen synthesis. The high level of prostaglandin E2 found in epithelial cell supernants after silica suggests that this molecule is involved in fibroblastic control in the lung.
Klien
J H
JH
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Adamson
I Y
IY
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005347:Fibroblasts / Q000166:cytology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D012822:Silicon Dioxide / Q000494:pharmacology*
D012822:Silicon Dioxide; D003094:Collagen; D015232:Dinoprostone; D007213:Indomethacin