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Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599-7365
Mortality associated with endotoxin shock is likely
mediated by Kupffer cells, alveolar macrophages, and circulating
neutrophils. Acute dietary glycine prevents mortality and blunts
increases in serum tumor necrosis factor-
(TNF-
) following
endotoxin in rats. Furthermore, acute glycine blunts activation of
Kupffer cells, alveolar macrophages, and neutrophils by activating a
glycine-gated chloride channel. However, in neuronal tissue, glycine
rapidly downregulates chloride channel function. Therefore, the
long-term effects of a glycine-containing diet on survival following
endotoxin shock were investigated. Dietary glycine for 4 wk improved
survival after endotoxin but did not improve liver pathology, decrease serum alanine transaminase, or effect TNF-
levels compared with animals fed control diet. Interestingly, dietary glycine largely prevented inflammation and injury in the lung following endotoxin. Surprisingly, Kupffer cells from animals fed glycine for 4 wk were no
longer inactivated by glycine in vitro; however, isolated alveolar
macrophages and neutrophils from the same animals were sensitive to
glycine. These data are consistent with the hypothesis that glycine
downregulates chloride channels on Kupffer cells but not on alveolar
macrophages or neutrophils. Importantly, glycine diet for 4 wk
protected against lung inflammation due to endotoxin. Chronic glycine
improves survival by unknown mechanisms, but reduction of lung
inflammation is likely involved.
endotoxin shock; Kupffer cells; alveolar macrophages; neutrophils; tumor necrosis factor-
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