INDUCTION OF PDGF RECEPTOR-ALPHA IN RAT MYOFIBROBLASTS DURING PULMONARY FIBROGENESIS IN-VIVO

Platelet-derived growth factor (PDGF) is a potent mitogen for mesenchy mal cells. Induction of the PDGF receptor-alpha (PDGF-R alpha) in vitr o enhances PDGF-induced mitogenesis and chemotaxis. Thus we investigat ed whether the PDGF-R alpha is induced in vivo during pulmonary fibrog enesis using a vanadium pentoxide (V2O5) model of lung injury. PDGF-R alpha mRNA expression was induced 24 h postinstillation. PDGF-R beta m RNA was constitutively expressed and did not increase. Western blottin g showed upregulation of PDGF-R alpha protein by 48 h, and immunohisto chemical analysis localized PDGF-R alpha primarily in mesenchymal cell s residing within fibrotic lesions. Upregulation of PDGF-R alpha in vi vo preceded mesenchymal cell hyperplasia (3-7 days) and collagen depos ition by day 15. Supernatants from alveolar macrophages treated with V 2P5 in vitro released upregulatory activity for PDGF-R alpha on cultur ed lung myofibroblasts, and this activity was blocked by the interleuk in-1-receptor antagonist. These data suggest that interleukin-1 beta-m ediated induction of PDGF-R alpha in vivo is important to lung myofibr oblast hyperplasia during fibrogenesis.