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This Article Full Text Full Text (PDF) All Versions of this Article: 285/6/L1312    most recent 00314.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Hastings, R. H. Articles by Deftos, L. J. Search for Related Content PubMed PubMed Citation Articles by Hastings, R. H. Articles by Deftos, L. J.

Amino-terminal and midmolecule parathyroid hormone-related protein, phosphatidylcholine, and type II cell proliferation in silica-injured lung

¹Research, Anesthesiology, and Medicine Services, Veterans Affairs San Diego Healthcare System, San Diego 92161; and ²Departments of Anesthesiology and Medicine, University of California San Diego, La Jolla, California 92093

Submitted 17 September 2002 ; accepted in final form 8 August 2003

Acute silica lung injury is marked by alveolar phospholipidosis and type II cell proliferation. Parathyroid hormone-related protein (PTHrP) 1-34 could have a regulatory role in this process because it stimulates phosphatidylcholine secretion and inhibits type II cell growth. Other regions of the PTHrP molecule may have biological activity and can also exert pulmonary effects. This study examined the temporal pattern for expression of several regions of PTHrP after silica lung injury and evaluated the effects of changes in expression on cell proliferation and lung phospholipids. Expression of all PTHrP regions fell at 4 days after injury. Reversing the decline in PTHrP 1-34 or PTHrP 67-86 with one intratracheal dose and four daily subcutaneous doses of PTHrP 1-34 or PTHrP 67-86 stimulated bronchoalveolar lavage disaturated phosphatidylcholine (DSPC) levels. Cell culture studies indicate that the peptides exerted direct effects on DSPC secretion by type II cells. Neither peptide affected type II cell proliferation with this dosing regimen, but addition of an additional intratracheal dose resulted in significant inhibition of growth, consistent with previous effects of PTHrP 1-34 in hyperoxic lung injury. These studies establish a regulatory role for PTHrP 1-34 and PTHrP 67-86 in DSPC metabolism and type II cell proliferation in silica injury. Growth inhibitory effects of PTHrP could interact with phospholipid stimulation by affecting type II cell numbers. Further studies are needed to explore the complex interactions of PTHrP-derived peptides and the type II cell response at various stages of silica lung injury.

adult respiratory distress syndrome; cell surface receptors; pulmonary surfactant; silicosis; type II pneumocyte

This article has been cited by other articles:

				R. H. Hastings, P. R. Montgrain, R. Quintana, Y. Rascon, L. J. Deftos, and E. Healy Cell cycle actions of parathyroid hormone-related protein in non-small cell lung carcinoma Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L578 - L585. [Abstract] [Full Text] [PDF]