PARATHYROID HORMONE-RELATED PROTEIN, AN AUTOCRINE REGULATORY FACTOR IN ALVEOLAR EPITHELIAL-CELLS

Alveolar epithelial cells in vivo, primary cultures of adult rat type II cells, and human A549 alveolar carcinoma cells express parathyroid hormone-related protein (PTHrP). Here we demonstrate that type II cell s and A549 cells also express the PTHrP receptor and that they exhibit differentiation-related responses to the amino-terminal PTHrP fragmen t, PTHrP-(1-34). PTHrP receptor expression in A549 cells was shown by detection of a 0.3-kb reverse transcriptase polymerase chain reaction product formed by primers specific for PTHrP receptor. In situ hybridi zation studies localized the site of production of PTHrP and PTHrP rec eptor mRNA in rat lung to cells with morphology and location typical o f type II cells. Primary cultures of such type II cells also expressed PTHrP receptor mRNA. Incubation with PTHrP-(1-34) stimulated disatura ted phosphatidylcholine (DSPC) synthesis in A549 cells and increased t he release of newly synthesized DSPC by cultured type II cells and A54 9 cells. In addition, PTHrP-(1-34) increased the number of lamellar bo dies per type II cell and increased their expression of alkaline phosp hatase in a dose-dependent manner. Thus PTHrP-(1-34) promoted a differ entiated type II cell phenotype. Since cultured type II cells, alveola r epithelial cells in vive, and A549 cells express PTHrP and the PTHrP receptor, PTHrP-(1-34) may be an autocrine regulatory factor in type II cells and lung cancer cells.