Proliferative characteristics of fibroblast lines derived from open lung biopsy specimens of patients with IPF (UIP).
We compared the doubling time of fibroblasts derived from idiopathic pulmonary fibrosis (usual interstitial pneumonia) (IPF [UIP]) lung tissues and control fibroblasts, cultured in usual growth medium, and examined the response of these fibroblasts to platelet-derived growth factor (PDGF) and prostaglandin E2 (PGE2). Ten fibroblast lines from open lung biopsy specimens of patients with IPF (UIP) and ten control fibroblast lines from surgically resected lung tissue of patients with limited lung diseases were established. The average doubling time of fibroblast lines was 32.0 +/- 6.0 h (mean +/- SD) in UIP and 33.2 +/- 10.4 h in controls, showing no difference between the two groups. To examine the responses of fibroblasts to PDGF and PGE2 and the differences between fibroblasts derived from fibrotic tissues with different intensity of fibrosis, lung specimens from five patients with IPF were subdivided into two groups, higher-intensity fibrotic lesions (H) and lower-intensity fibrotic lesions (L). The fibroblast lines were established separately. 3H-thymidine uptake with or without PDGF or PGE2 was examined. Results were expressed as the index of thymidine incorporation into the fibroblasts. There were no differences in the doubling times and the responses to PDGF and PGE2 between H and L. There were no differences between control and H regarding their response to PDGF. In response to PGE2, the growth inhibition for H was significantly decreased compared with the control (p less than 0.05). There was no difference in growth inhibition between H and L. The finding that PGE2 inhibits fibroblast proliferation less in UIP lung tissue suggests that fibroblasts from UIP were functionally altered cells or, to some extent, out of normal regulation. These results suggest an abnormal proliferation of fibroblasts observed in IPF (UIP).
Mio
T
T
Second Department of Internal Medicine, Chest Disease Research Institute, Kyoto University, Japan.
Nagai
S
S
Kitaichi
M
M
Kawatani
A
A
Izumi
T
T
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000473:pathology*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D010982:Platelet-Derived Growth Factor; D014316:Tritium; D015232:Dinoprostone; D013936:Thymidine