Interferon-gamma modulates lung macrophage production of PDGF-BB and fibroblast growth

Platelet-derived growth factor (PDGF) is a potent mediator of fibroblast proliferation and chemotaxis. We have studied here the cytokine interferon-gamma (IFN-gamma) which is known to prime macrophages for increased PDGF production. Thus, we postulated that IFN-gamma would act as a positive regulator of PDGF-BB secretion by rat alveolar macrophages, and in addition we asked whether or not the IFN-gamma (a known anti-mitogenic cytokine) would block the growth response of primary lung fibroblasts to the PDGF-BB. Macrophages incubated with IFN-gamma or iron spheres alone for 24 h secreted 2.5-fold more PDGF-BB than control macrophages incubated in serum-free medium. Preincubation of macrophages with IFN-gamma prior to the addition of iron spheres synergistically increased PDGF-BB production 2-10-fold after 24 h. In contrast, when IFN-gamma was added to quiescent rat lung fibroblasts (RLFs) in the presence of PDGF-BB, the cytokine induced a concentration-dependent decrease in cell growth, while IFN-gamma alone did not affect proliferation. [I-125]PDGF-BB receptor assays showed that neither preincubation nor coincubation of RLF with IFN-gamma affected PDGF-BB binding to its receptors.