In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 42, No. 1 ( 1987-07-01), p. 51-60
Abstract:
Pulmonary fibrosis is characterized by an alteration in lung collagen synthesis and deposition, as well as by increased fibroblast proliferation. It is also characterized by an intermittent influx of immune and inflammatory cells in the lung. To investigate the nature of the target cell in this disorder, we established a series of primary lines of human adult lung fibroblasts and studied the effect of mediators released from activated normal human alveolar macrophages (AM) and peripheral blood monocytes (PBM) on the proliferation of both normal lung fibroblasts and fibroblasts established from lung tissue of patients with active fibrosis. Our data show that monocyte supernatants containing a 15-18 kD monokine from either AM or PBM inhibits growth of logarithmic phase proliferating lung fibroblasts in a dose-dependent manner. This effect can be entirely abrogated by treating the fibroblasts with indomethacin and is reconstituted by adding exogenous PGE2. A study of the kinetics of this interaction shows that exposure to monocyte supernatant for 30 min to 1 hr is sufficient to cause significant inhibition of fibroblast proliferation and that this effect can be halted, but not reversed, at any stage by incubation with indomethacin. We also show that fibroblasts derived from patients with pulmonary fibrosis are affected more quickly by exposure to the mediators, although the final extent of inhibition seen at each concentration of mediators is similar in normal and “fibrotic” fibroblasts. These studies indicate that activated AM or PBM release cytokines (including IL-1) which inhibit the growth of proliferating normal and fibrotic fibroblasts through activation of the intrinsic arachidonic acid pathway of this cell and also that this effect requires a continuous activation of this pathway to be fully expressed.
Type of Medium:
Online Resource
ISSN:
0741-5400
,
1938-3673
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
1987
detail.hit.zdb_id:
2026833-6
SSG:
12
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