Parathyroid hormone-related protein response to hyperoxic lung injury.
Parathyroid hormone-related protein (PTHrP) is a growth inhibitor for alveolar type II cells. Type II cell proliferation after lung injury from 85% oxygen is regulated, in part, by a fall in lung PTHrP. In this study, we investigated lung PTHrP after injury induced by >95% oxygen in rats and rabbits. In adult rats, lung PTHrP rose 10-fold over controls to 6,356 +/- 710 pg/ml (mean +/- SE) at 48 h of hyperoxia. Levels fell to 299 +/- 78 pg/ml, and staining for PTHrP mRNA was greatly reduced at 60 h (P < 0.05), the point of most severe injury and greatest pneumocyte proliferation. In adult rabbits, lung PTHrP peaked at 3,289 +/- 230 pg/ml after 64 h of hyperoxia with 24 h of normoxic recovery and then dropped to 1,629 +/- 153 pg/ml at 48 h of recovery (P < 0.05). Type II cell proliferation peaked shortly after the fall in PTHrP. In newborn rabbits, lavage PTHrP increased by 50% during the first 8 days of hyperoxia, whereas type II cell growth decreased. PTHrP declined at the LD(50), concurrent with increased type II cell division. In summary, lung PTHrP initially rises after injury with >95% hyperoxia and then falls near the peak of injury. Changes in PTHrP are temporally related to type II cell proliferation and may regulate repair of lung injury.
Hastings
Randolph H
RH
Research, Anesthesiology, and Medicine Services, Veterans Affairs San Diego Healthcare System, San Diego, California 92161, USA. rhhastings@ucsd.edu
Ryan
Rita M
RM
D'Angio
Carl T
CT
Holm
Bruce A
BA
Patel
Alka
A
Quintana
Rick
R
Biederman
Elana
E
Burton
Douglas W
DW
Deftos
Leonard J
LJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002455:Cell Division / Q000187:drug effects; D018496:Hyperoxia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010100:Oxygen / Q000633:toxicity; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms
D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D010100:Oxygen