Calorie-related rapid onset of alveolar loss, regeneration, and changes in mouse lung gene expression.
Calorie restriction, followed by ad libitum refeeding, results, respectively, in loss and regeneration of pulmonary alveoli. We now show 35% of alveoli are lost within 72 h of onset of calorie restriction ((2/3) decreased daily chow intake), and an additional 12% of alveoli are lost over a subsequent 12 days of calorie restriction. Tissue necrosis was not seen. Within 72 h of refeeding, after 15 days of calorie restriction, the number of alveoli returns to precalorie restriction values. Microarray lung gene profiling, in conjunction with Western and RNase protection assay, demonstrate an increase of granzyme and caspase gene expression 2-3 h after onset of calorie restriction. By 12 h, granzyme and caspase expression is no longer increased, but tumor necrosis factor death receptor expression is elevated. At 336 h, Fas death receptor expression is increased. Because granzymes are found only in cytotoxic lymphocytes (CTLs) and natural killer (NK) cells, we suggest calorie restriction activates these cells, initiating a series of molecular events that results in alveolar destruction. The evidence of involvement of CTLs and NK cells and the absence of necrosis are similar to alveolar destruction in chronic obstructive pulmonary disease.
Lung Biology Laboratory, Box 571481, Preclinical Science Bldg., GM-12, Georgetown Univ. School of Medicine, 3900 Reservoir Road, NW, Washington, DC 20057-1481. massarod@georgetown.edu
Donald
D
Massaro
Gloria DeCarlo
GD
Massaro
Alex
A
Baras
Eric P
EP
Hoffman
Linda Biadasz
LB
Clerch
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000235:genetics; D004038:Diet, Reducing / Q000009:adverse effects; D002149:Energy Intake; D005786:Gene Expression Regulation; D016678:Genome; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D011650:Pulmonary Alveoli / Q000473:pathology* / Q000502:physiology*; D012038:Regeneration
D020169:Caspases