Asbestos-induced alveolar injury. Evidence for macrophage-derived PDGF as a mediator of the fibrogenic response.

54$ 33rd Annual Thomas L Petty Aspen Lung Conference 1 Crapo JD, Barry BE, Foscue HA, Shelburne J. Structural and biochemical changes in rat lungs occuring during exposure to lethal and adaptive doses of oxygen. Am Rev Respir Dis 1980; 112:123-43 2 Durr BA, Dubaybo BA, Thet LA. Repair of chronic hyperoxic lung injury: changes in lung ultrastructure and matrix. Exp Mol Pathol 1987; 47:219-40 3 Ross B, Baines EW, Bowen-Pope DF. The biology of plateletderived growth factor. Cell 1986; 46:155-69 4 Fabisiak JP, Evans JN, Kelley J. Increased expression of PDCF-B (c-six) mRNA in rat lung precedes DNA synthesis and tissue repair during chronic hyperoxia. Am Rev Respir Dis 1989; 1:181-89 5 Aviv H, Leder P Purification of biologically active globin messenger RNA by chromatography on oligo-thymidylic acid-cellulose. Proc Natl Acad Sci USA 1972; 69:1408-12 6 Raines EW, Dower SK, Ross B. lnterleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDCF-AA. Science 1989; 243:393-96 7 Paulsson Y, Austgulen R, Hofsli E, Heldin C-H, Westermark B, Nissen-Moyer J. Tumor necrosis factor-induced expression of platelet-derived growth factor A-chain messenger RNA in fibroblasts. Exp Cell Res 1989; 180:490-96 FIGURE 1. Secretion of a platelet-derived growth factor homologue by alveolar macrophages (MOs) following in vivo or in vitro activation via the phagocytosis of chrysotile asbestos or carbonyl iron. Macrophages activated in vivo were lavaged from animals 1 wk post exposure and cultured for 24 h. Macrophages lavaged from unexposed animals were activated in vitro by adding particulate suspensions to plastic-adherent macrophages for 24 h. Macrophageconditioned medium was concentrated 100-fold, acidified to 1 M acetic acid for 1 h, and fractionated on a Superose 12 FPLC gel filtration column. Neutralized fractions were tested for PDGF by using an enzyme immunoassay. The data represent mean ± SEM of 3 separate experiments.