PLATELET-DERIVED GROWTH-FACTOR CAUSES PULMONARY CELL-PROLIFERATION AND COLLAGEN DEPOSITION IN-VIVO

Platelet-derived growth factor (PDGF) is postulated to play a role in the pathophysiology of pulmonary fibrosis. Recombinant human PDGF-BB a dministered as a single intratracheal injection in rats causes an incr ease in peribronchial and perivascular stromal cells on days 2 and 3 a fter injection as evaluated by hematoxylin and eosin histology and 5-b romodeoxyuridine incorporation. Proliferation of bronchial epithelial cells and arterial smooth muscle cells, although not evident by routin e histological examination alone, is detected on days 2 and 3 by incre ased 5-bromodeoxyuridine incorporation. A mild increase in 5-bromodeox yuridine labeling is observed in peripheral alveolar parenchyma after injection of PDGF. The proliferative peribronchial and perivascular me senchymal cells appear by light microscopic and ultrastructural criter ia to be fibroblasts that are immunoreactive for vimentin but negative for alpha-smooth muscle actin and desmin. Daily intratracheal injecti on of PDGF-BB for 3 days causes a slightly more pronounced peribronchi al and perivascular spindle cell proliferation accompanied by collagen deposition as evaluated by Masson's trichrome stain. PDGF-induced inc reases in cellularity and collagen resolve within 5 days after the las t PDGF injection. In conclusion, intratracheal injection of PDGF-BB ca uses transient proliferation of pulmonary mesenchymal and epithelial c ells accompanied by collagen deposition.