INTERFERON-GAMMA MODULATES LUNG MACROPHAGE PRODUCTION OF PDGF-BB AND FIBROBLAST GROWTH

Platelet-derived growth factor (PDGF) is a potent mediator of fibrobla st proliferation and chemotaxis. We have studied here the cytokine int erferon-gamma (IFN-gamma) which is known to prime macrophages for incr eased 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 fi broblasts 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 ma crophages 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 I FN-gamma was added to quiescent rat lung fibroblasts (RLFs) in the pre sence of PDGF-BB, the cytokine induced a concentration-dependent decre ase 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 re ceptors.