Dietary glycine blunts lung inflammatory cell influx following acute endotoxin.
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-alpha (TNF-alpha) 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-alpha 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.
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599-7365, USA. wheelmi@med.unc.edu
M D
MD
Wheeler
M L
ML
Rose
S
S
Yamashima
N
N
Enomoto
V
V
Seabra
J
J
Madren
R G
RG
Thurman
D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D019587:Dietary Supplements; D004334:Drug Administration Schedule; D005998:Glycine / Q000008:administration & dosage*; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium; D005998:Glycine