INDUCTION OF THE LUNG MYOFIBROBLAST PDGF RECEPTOR SYSTEM BY URBAN AMBIENT PARTICLES FROM MEXICO-CITY

Platelet-derived growth factor (PDGF) and its receptor system regulate mesenchymal cell proliferation. We recently reported that emission-so urce fly-ash particles and asbestos fibers induce the PDGF alpha-recep tor through a macrophage-dependent pathway, and upregulation of this r eceptor greatly enhances the mitogenic response of lung myofibroblasts to PDGF (Lindroos and colleagues, Plm. J. Respir. Cell Mel. Biol. 199 7;16:283-292). In the present study we investigated the effect of part iculate matter less than or equal to 10 mu m in size (PM10) from the s outhern, central, and northern regions of Mexico City on PDGF receptor induction and compared these urban, ambient particles with Mt. St. He len's volcanic ash particles as a negative control. All Mexico City PM 10 samples, but not volcanic ash, stimulated rat alveolar macrophages to secrete a soluble, upregulatory factor(s) for the PDGF alpha-recept or on early passage rat lung myofibroblasts. The macrophage-derived up regulatory activity was blocked by the interleukin (IL)-1 receptor ant agonist. The ability of PM10 to stimulate IL-1 beta release was blocke d in part by a recombinant endotoxin neutralizing protein (rENP). Lipo polysaccharide/endotoxin (LPS) and vanadium, both constituents that we re present within these PM10 samples, also stimulated macrophages to s ecrete factor(s) that upregulated PDGF-R alpha on lung myofibroblasts. Direct exposure of myofibroblasts to PM10 also elicited upregulation of the PDGF alpha-receptor, and this effect was blocked by rENP and mi micked by LPS, but not vanadium. These findings suggest that PM10 part icles induce expression of the PDGF receptor system through macrophage -dependent and -independent mechanisms involving endotoxin and metals.