CHRYSOTILE ASBESTOS UP-REGULATES GENE-EXPRESSION AND PRODUCTION OF ALPHA-RECEPTORS FOR PLATELET-DERIVED GROWTH-FACTOR (PDGF-AA) ON RAT LUNGFIBROBLASTS

PDGF isoforms have been postulated to serve as mediators of fibroblast proliferation and chemotaxis during lung fibrogenesis induced by asbe stos inhalation. We have studied the interaction of chrysotile asbesto s fibers with rat lung fibroblasts (RLF) in vitro and the consequent c hanges in PDGF receptor mRNA expression, PDGF binding, and mitogenic a ctivity of PDGF isoforms. Northern blot analysis revealed that mRNA fo r the PDGF-receptor alpha subtype (PDGF-Ralpha) on RLF was upregulated after a 24-h exposure to asbestos in culture (0.5-15 mug fibers/cm2). [I-125]pDGF-BB receptor assays showed that normal RLF possess mainly PDGF-Rbeta and a paucity of PDGF-Ralpha. In agreement with the Norther n data, saturation binding of [I-125] PDGF-BB to RLF exposed to asbest os demonstrated an approximately 40% increase in binding sites accompa nied by a twofold decrease in receptor affinity. Treating asbestos-exp osed RLF with PDGF-AA, which binds only PDGF-Ralpha, blocked the PDGF binding sites that were upregulated by fiber exposure. PDGF-AA had inc reased mitogenic potency for fiber-exposed RLF, but PDGF-BB was a less potent mitogen for these RLF. Nonfibrogenic carbonyl iron spheres ind uced similar changes in PDGF growth responses. These data show that in organic particulates alter the PDGF-Ralpha population on RLF without s ignificant change in PDGF-Rbeta.