Acute alcohol intoxication and gadolinium chloride attenuate endotoxin-induced release of CC chemokines in the rat.
This work tests the hypotheses that Kupffer cells are a major source of CC-chemokines (MIP-1alpha, MCP-1, RANTES) during acute endotoxemia and that acute ethanol intoxication modulates Escherichia coli lipopolysaccharide (LPS, 1 mg/Kg, i.v.)-induced chemokine release in the rat. LPS stimulated the release of CC-chemokines into the circulation, hepatic sequestration of leukocytes and liver injury. LPS-induced serum chemokines peaked at 1-3 h and could not be detected at 24-h posttreatment. Splenectomy significantly suppressed LPS-induced RANTES release, but not MIP-1alpha and MCP-1. Kupffer cell depletion by gadolinium chloride or acute ethanol intoxication significantly attenuated LPS-induced CC-chemokine release and hepatic injury. Hepatic sequestration of leukocytes during endotoxemia was also suppressed by acute ethanol. LPS downregulated the expression of MIP-1alpha and MCP-1 mRNAs and upregulated RANTES mRNA in Kupffer cells at 3-h post endotoxin. The expression of mRNAs was further suppressed in ethanol plus the LPS-treated group. Ethanol also suppressed the LPS-mediated priming of Kupffer cells for enhanced CC-chemokine release in vitro. Ethanol alone significantly upregulated the expression of CC-chemokine mRNA, and primed the Kupffer cells for enhanced RANTES release. CC-chemokine release and mRNA expression in hepatic sinusoidal endothelial cells were not significantly altered by ethanol, except for MCP-1 release. These data show that acute ethanol may be beneficial in tissue injury during acute endotoxemia.
Bukara
M
M
Department of Physiology and NIAAA-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Ceniter, New Orleans 70112, USA.
Bautista
A P
AP
D000208:Acute Disease; D000410:Alanine Transaminase / Q000378:metabolism; D000435:Alcoholic Intoxication / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000378:metabolism*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000378:metabolism*; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins; D005434:Flow Cytometry; D005682:Gadolinium / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013156:Splenectomy
D001427:Bacterial Toxins; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D004731:Endotoxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D005682:Gadolinium; C027538:heat-labile enterotoxin, E coli; D000410:Alanine Transaminase