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Am J Physiol Lung Cell Mol Physiol (March 15, 2002). doi:10.1152/ajplung.00035.2002
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Articles in PresS, published online ahead of print March 15, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00035.2002
Submitted on January 23, 2002
Accepted on March 7, 2002

Lung alveoli: endogenous programmed destruction and regeneration

Gloria De Carlo Massaro1, Svetlana Radaeva2, Linda Biadasz Clerch1, and Donald Massaro1*

1 Lung Biology, Georgetown University School of Medicine, Washington, DC, USA
2 NIAA- Flow Lab, National Institutes of Health, Rockville, MD, USA

* To whom correspondence should be addressed. E-mail: massarog{at}georgetown.edu.

Mammalian alveoli, complex architectural and cellular units whose dimensions are linked to the organism's oxygen consumption (VO2), are thought to be destroyed only by disease and not to spontaneously regenerate. Calorie restriction of adult mammals lowers VO2, ad libitum refeeding returns VO2 to pre-calorie restriction values. We took advantage of these relationships and tested the hypothesis in adult mice that calorie restriction (2/3 reduction for two weeks) followed by ad libitum refeeding (three weeks) would, respectively, cause alveolar destruction and regeneration. Calorie restriction diminished alveolar number 55% and alveolar surface area 25%. Refeeding fully reversed these changes. Neither manipulation altered lung volume. Within 72 hr, calorie restriction increased alveolar-wall cell apoptosis and diminished (~20%) lung DNA amount. By 72 hr of refeeding, alveolar-wall cell replication increased and lung DNA rose to amounts in mice never calorie restricted. We conclude, adult mice have endogenous programs to destroy and regenerate alveoli thereby raising, respectively, the danger of inappropriate activation, but the possibility of therapeutic induction, if similar programs exist in humans.




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