ALVEOLAR EPITHELIAL-CELLS EXPRESS AND SECRETE PARATHYROID HORMONE-RELATED PROTEIN

Parathyroid hormone-related protein (PTHrP) was discovered as a hyperc alcemia-inducing product of malignant cells and has since been demonst rated to be a product of many tissues. Although it is robustly express ed in fetal lung, PTHrP expression has not been assigned to alveolar e pithelial cells in adult lung. We have shown that PTHrP is expressed i n the adult rat lung and by cultured rat alveolar type LT epithelial c ells with sensitive and specific immunoassays and immunohistochemical techniques. Immunoassay of cell extracts demonstrated that freshly iso lated type II cells contained PTHrP (136 pg/10(7) cells), whereas fres hly isolated alveolar macrophages and cultured macrophages did not exp ress PTHrP. Cultured type II cells secreted PTHrP into medium, 202 +/- 11 fg PTHrP/mu g cell protein in 24 h. Basal secretion remained stabl e up to 7 days in culture. Treatment with phorbol myristate acetate or 1-oleoyl-2-acetyl sn-glycerol produced a dose-related, 2- to 4-fold i ncrease in PTHrP secretion. However, forskolin, ionomycin, ATP, phenyl ephrine, capsaicin, and bradykinin had no effect. Thus, PTHrP secretio n appeared to be regulated by a protein kinase C-dependent pathway. PT HrP could also be demonstrated in pulmonary lavage fluid. Although the function of PTHrP in the adult lung is unknown, it could involve cont rol of cell growth and differentiation or control of surfactant lipid secretion. Further studies are necessary to elucidate the function of PTHrP in the lung.