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Blood and lung mononuclear cell inhibition of fibroblast growth in sarcoidosis
Abstract:
A defect in mononuclear cell inhibition of fibroblast growth may be important in the pathogenesis of tissue fibrosis in sarcoidosis. To test this hypothesis, supernatants were prepared from unstimulated and phytohemagglutinin (PHA) stimulated peripheral blood and nonadherent lung mononuclear cells of patients with sarcoidosis. The effect of these supernatants on human lung fibroblast log phase growth was compared with the effect of similar supernatants from normal persons and patients with other lung diseases. Supernatants from normal persons and the majority of patients with sarcoidosis had similar effects on fibroblast growth. Unstimulated blood and nonadherent lung mononuclear cells had no consistent effect on fibroblast growth, whereas PHA stimulated cells inhibited fibroblast growth in a dose-dependent fashion. However, unlike that in normal persons, the blood and/or lung mononuclear cells from approximately one third of the patients with sarcoidosis appeared to be activated in vivo because supernatants from these cells inhibited fibroblast growth without in vitro mitogen stimulation. Spontaneous inhibition of fibroblast growth was not seen in supernatants from blood or nonadherent lung mononuclear cells from patients with other lung diseases. Age, sex, lavage cell yield and differential, peripheral lymphocyte count, and percentage of activated T-lymphocytes did not differentiate patients whose mononuclear cells spontaneously inhibited fibroblast growth from those patients whose cells did not. However, patients whose lung mononuclear cells spontaneously inhibited fibroblast growth had fewer pulmonary function abnormalities than did patients whose cells did not.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Mononuclear cells from some sarcoidosis patients can spontaneously inhibit fibroblast growth, suggesting a role in tissue fibrosis. This spontaneous inhibition was not observed in other lung diseases.
Area of Science:
- Immunology
- Pulmonology
- Cell Biology
Background:
- Tissue fibrosis in sarcoidosis may involve defects in mononuclear cell regulation of fibroblast growth.
- Understanding the interaction between immune cells and fibroblasts is crucial for sarcoidosis pathogenesis.
Purpose of the Study:
- To investigate the hypothesis that impaired mononuclear cell inhibition of fibroblast growth contributes to sarcoidosis pathogenesis.
- To compare fibroblast growth inhibition by mononuclear cells from sarcoidosis patients versus healthy individuals and those with other lung diseases.
Main Methods:
- Preparation of supernatants from unstimulated and phytohemagglutinin (PHA)-stimulated peripheral blood and lung mononuclear cells.
- Assay of supernatant effects on human lung fibroblast proliferation.
- Comparison between sarcoidosis patients, normal individuals, and patients with other lung diseases.
Main Results:
- PHA-stimulated mononuclear cells inhibited fibroblast growth in a dose-dependent manner in both normal and sarcoidosis groups.
- Approximately one-third of sarcoidosis patients exhibited spontaneous fibroblast growth inhibition by mononuclear cells, independent of in vitro stimulation.
- Spontaneous inhibition was not observed in mononuclear cells from patients with other lung diseases.
- Fewer pulmonary function abnormalities were noted in sarcoidosis patients with spontaneous mononuclear cell inhibition.
Conclusions:
- A subset of sarcoidosis patients demonstrates in vivo activated mononuclear cells capable of spontaneous fibroblast growth inhibition.
- This spontaneous inhibition may play a role in the fibrotic processes characteristic of sarcoidosis.
- Further research is warranted to elucidate the mechanisms and clinical implications of this finding.
