PARATHYROID HORMONE-RELATED PROTEIN, AN AUTOCRINE GROWTH INHIBITOR OFALVEOLAR TYPE-II CELLS

We investigated autocrine effects on growth by decreasing endogenous P THRP in rat type II cells. Cultured cells were incubated with antibodi es against PTHRP-(1-34) (8B12) or PTHRP-(109-141) (9H7) or an irreleva nt antibody (1 mu g/ml) for 3 days. Conditioned media from the irrelev ant antibody group contained 143 +/- 8 fg PTHRP/ 100,000 cells. The 8B 12 and 9H7 reduced levels to 45 +/- 8 and 88 +/- 16 fg PTHRP/100,000 c ells, respectively (n = 4 cell isolations, P < 0.05). Cells treated wi th the PTHRP antibodies nearly tripled in number. The irrelevant antib ody had no effect on growth. Exogenous PTHRP-(1-34) (2.5 nM) blocked t he growth-stimulating effect of 9H7. Instilled intratracheal 8B12 and 9H7 induced expression of proliferating cell nuclear antigen in cluste rs of alveolar cells in rats. Clustered cells expressed surfactant apo proteins and cytokeratin 19. These data suggest that endogenous PTHRP- (1-34) inhibits proliferation of type II cells in vivo and in vitro.