BRONCHOALVEOLAR LAVAGE FLUID FROM IMMATURE RATS WITH HYPEROXIA-INDUCED AIRWAY REMODELING IS MITOGENIC FOR AIRWAY SMOOTH-MUSCLE

We previously demonstrated that hyperoxia-exposed immature rats develo p airway smooth muscle layer thickening; this remodeling appears parti ally attributable to smooth muscle hyperplasia. In this study, we test ed the hypothesis that excess mitogenic activity for airway smooth mus cle cells is present within the lungs of hyperoxia-exposed immature ra ts. We assessed the proliferative effect of bronchoalveolar lavage (BA L) fluid from air- and O-2-exposed animals on cultured rat tracheal sm ooth muscle cells. BAL fluids from air- or O-2-exposed immature rats i ncreased DNA synthesis ([H-3]-thymidine incorporation at 24 h of incub ation) and cell number (compared with DMEM-treated control cells, at 2 days of incubation), but BAL fluid from O-2-exposed animals had signi ficantly greater mitogenic effects. This excess mitogenic activity was lipid inextractable and was ablated by trypsin digestion, indicating that at least one polypeptide growth factor was responsible; molecular sieve fractionation demonstrated a molecular weight of > 10 kD. Becau se platelet-derived growth factor (PDGF) has been identified in other models of hyperoxia exposure, we tested the further hypothesis that PD GF contributes to the observed excess mitogenic activity. Addition of neutralizing anti-PDGF antibodies to BAL-stimulated smooth muscle cult ures did not reduce BAL fluid-induced mitogenesis. These data indicate that the lungs of O-2-exposed rats contain excess mitogenic activity for airway smooth muscle, attributable to non-PDGF polypeptide growth factors. It is conceivable that this abnormal mitogenic activity contr ibutes to O-2-induced airway smooth muscle remodeling observed in imma ture rats in vivo.