Modulation of f-met-leu-phe induced chemotactic activity and superoxide production by neutrophils during chronic ethanol intoxication.
Chronic alcohol consumption has been associated with increased migration of neutrophils into liver that could contribute to the development of alcoholic liver disease. Mild endotoxemia may be at least partially responsible for this condition since endotoxemia was shown to be present in virtually all chronic alcoholics. This study examines the release of superoxide anion and chemotactic activity by Kupffer cells and sequestered hepatic as well as blood neutrophils during chronic alcohol intoxication (16 weeks) alone, and following an intravenous injection of Escherichia coli lipopolysaccharide (LPS) (1 mg/kg) 3 hr before cell isolation. Chronic ethanol consumption increased the total neutrophil yield per liver, but did not change the f-met-leu-phe induced chemotactic activity by both hepatic and blood neutrophils. However, the combined insults of ethanol and LPS increased the chemotactic activity and superoxide anion generation by these cells. Plasma from ethanol-fed rats was highly chemotactic to syngeneic normal rat neutrophils. This activity was increased 1.75-fold in the plasma obtained from chronic ethanol plus endotoxin-injected rats. The chemotactic activity of Kupffer cells was not significantly modulated during ethanol intoxication plus endotoxin treatment. The f-met-leu-phe-induced superoxide anion release by Kupffer cells was enhanced after LPS treatment. Chronic ethanol consumption did not induce any effect on this parameter. These observations suggest that functional alterations in neutrophils during chronic ethanol intoxication may contribute to hepatic injury.
Bautista
A P
AP
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
D'Souza
N B
NB
Lang
C H
CH
Spitzer
J J
JJ
D000435:Alcoholic Intoxication / Q000276:immunology*; D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D004731:Endotoxins / Q000097:blood; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism*
D004731:Endotoxins; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine