Hyperoxia and nitric oxide reduce surfactant components (DSPC and surfactant proteins) and increase apoptosis in adult and fetal rat type II pneumocytes.
Nitric oxide (NO) alone or in conjunction with hyperoxia can have protective or detrimental effects on the lung. Our hypothesis was that hyperoxia in conjunction with NO would result in increased cellular dysfunction and apoptotic cell death in adult and fetal Type II pneumocytes (TIIP) in a dose-dependent manner. The TIIP were obtained from adult and 19-day fetal rat lungs. The TIIP were then exposed to 100, 200 and 500 micro M of the NO-donor, Glyco-SNAP-2, alone or in conjunction with 95% oxygen for 24 h. While low-dose NO exposure alone did not increase cytotoxicity, in conjunction with hyperoxia, there was a significant dose-dependent increase in apoptotic cell death of adult TIIP as well as fetal TIIP. Choline incorporation into disaturated phosphatidylcholine was markedly decreased in adult TIIP while the fetal TIIP had similar values as controls. However, the mRNAs of surfactant proteins A, B and C as well as iNOS were significantly reduced in fetal TIIP. Exogenous peroxynitrite also increased nitrotyrosine formation in fetal TIIP as did hyperoxia and NO. The effect of hyperoxia and NO could be abrogated with catalase and superoxide dismutase. These findings may have significant clinical implications in the use of NO in premature infants.
Bhandari
V
V
Department of Pediatrics, Albert Einstein Medical Center, 5501 Old York Road, Philadelphia, PA 19141, USA. vineet.bhandari@yale.edu
Johnson
L
L
Smith-Kirwin
S
S
Vigliotta
G
G
Funanage
V
V
Chander
A
A
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D005260:Female; D008168:Lung / Q000196:embryology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen / Q000494:pharmacology*; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D010100:Oxygen