TRANSFORMING GROWTH-FACTOR-BETA ACTIVITY IN SHEEP LUNG LYMPH DURING THE DEVELOPMENT OF PULMONARY-HYPERTENSION

Chronic pulmonary hypertension is associated with extensive structural remodeling of the pulmonary arterial bed. The structural changes in the arterial walls include increased production of extracellular matrix components and smooth muscle cell hypertrophy, changes that have been similarly induced by transforming growth factor-β (TGF-β) in culture. In the present study, experiments were performed to determine whether TGF-β is present in sheep lung lymph, and whether TGF-β levels were altered in an animal model of chronic pulmonary hypertension induced by continuous air embolization. Several standard biological assays for TGF-β activity were used for these determinations including soft agar assays, inhibition of epithelial cell proliferation, and a TGF-β-specific radioreceptor assay. In each case, control lung lymph contained high concentrations of TGF-β (100 ng/ml) which required transient acidification for detection. Samples of lung lymph from hypertensive sheep showed a transient and early two- to threefold increase in concentrations of latent TGF-β. This activity could be partially blocked by TGF-β antibodies. These studies indicate that sheep lung lymph contains TGF-β and that the level of TGF-β increases early during the development of pulmonary hypertension. Thus, TGF-β may contribute to the development of the structural changes in the pulmonary arteries that occur during the onset of chronic pulmonary hypertension.