Parathyroid hormone-related protein, an autocrine growth inhibitor
of alveolar type ii cells.
Hastings, Randolph H., Daphne Summers-Torres, Burt Yaszay, James
Lesueur, Douglas W. Burton, and Leonard J. Deftos.
Anesthesiology and Medicine Services, Department of Veterans
Affairs Medical Center, San Diego, CA; Departments of Anesthesiology
and Medicine, University of California San Diego
APStracts 3:0194L, 1996.
Parathyroid hormone-related protein (PTHrP) is an autocrine regulator
of differentiation for type II pneumocytes (Am J Physiol, 270:L353
-L361, 1996). We investigated autocrine effects on growth by
decreasing endogenous PTHrP in rat type II cells. Cultured cells were
incubated with antibodies against PTHrP 1-34 (8B12), PTHrP 109-141
(9H7), or an irrelevant antibody (1 g/ml) for three days. Conditioned
media from the irrelevant antibody group contained 143 8 fg
PTHrP/100,000 cells. 8B12 and 9H7 reduced levels to 45 8* and 88 16*
fg PTHrP/100,000 cells, respectively (n = 4 cell isolations, *P
< 0.05). Cells treated with the PTHrP antibodies nearly
tripled in number. The irrelevant antibody had no effect on growth.
Exogenous PTHrP 1-34 (2.5 nM) blocked the growth-stimulating effect
of 9H7. Instilled intratracheal 8B12 and 9H7 induced expression of
proliferating cell nuclear antigen in clusters of alveolar cells in
rats. Clustered cells expressed surfactant apoproteins and
cytokeratin 19. These data suggest that endogenous PTHrP 1-34
inhibits proliferation of type II cells in vivo and in vitro.
Received 7 August 1996; accepted in final form 14 October 1996.
APS Manuscript Number L256-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996