Am. J. Respir. Cell Mol. Biol., Volume 19, Number 3, September, 1998 462-469

Altered Alveolar Macrophage Function in Calorie-restricted Rats

Wumin Dong, MaryJane K. Selgrade, M. Ian Gilmour, Robert W. Lange, Patricia Park, Michael I. Luster, and Frank W. Kari

Immunotoxicology Branch, United States Environmental Protection Agency, Research Triangle Park; Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill; Nutrition and Toxicology Group, Laboratory of Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; and Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia

Alveolar macrophage functions associated with clearance of bacteria from the lung were assessed in male Fischer 344 rats maintained on a 25% calorie-restricted diet. Calorie-restricted and ad libitum-fed (control) rats were exposed to concentrations of ozone known to compromise phagocytic function of alveolar macrophages. Ozone suppressed alveolar macrophage phagocytosis of latex beads in vitro in ad libitum-fed rats, but not in calorie-restricted rats. In fact, caloric restriction enhanced phagocytic function in both control and ozone-exposed animals. Ad libitum-fed rats exposed to ozone and challenged with Streptococcus zooepidemicus experienced a prolonged infection and influx of polymorphonuclear leukocytes (PMN), whereas calorie-restricted rats exposed to ozone cleared the bacteria in 24 h without an inflammatory response. Bacterial endotoxin-stimulated in vitro production of nitric oxide and tumor necrosis factor (TNF)- as well as expression of TNF- and interleukin-6 messenger RNAs were all lower in alveolar macrophages isolated from calorie-restricted rats. Together, the data suggest that caloric restriction enhances resistance to gram-positive bacteria, while lowering the production of proinflammatory mediators elicited by endotoxin, a component of gram-negative bacteria. Although increased bacterial resistance is considered beneficial, reduction in the lung's ability to induce inflammatory mediators can have both positive and pathophysiologic consequences.

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