Format

Send to

Choose Destination
Gastroenterology. 1998 Aug;115(2):443-51.

Alcohol causes both tolerance and sensitization of rat Kupffer cells via mechanisms dependent on endotoxin.

Author information

1
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology,University of North Carolina at Chapel Hill, North Carolina, USA.

Abstract

BACKGROUND & AIMS:

Ethanol causes both tolerance and sensitization of Kupffer cells. This study was designed to evaluate temporal effects of ethanol in an attempt to understand this paradox.

METHODS:

Rats were given ethanol (4 g/kg body wt) intragastrically, and Kupffer cells were isolated 0-48 hours later. After addition of lipopolysaccharide (LPS), intracellular calcium concentration ([Ca2+]i) was measured using a microspectrofluorometer with the fluorescent indicator fura-2, and tumor necrosis factor alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay. CD14 was evaluated by Western and Northern analysis.

RESULTS:

Two hours after ethanol administration, the LPS-induced increase in [Ca2+]i and TNF-alpha release by Kupffer cells was diminished by 50%, and these parameters were reciprocally enhanced twofold at 24 hours. Sterilization of the gut with antibiotics blocked all effects of ethanol on [Ca2+]i and TNF-alpha release completely. Twenty-four hours after ethanol, CD14 in Kupffer cells was elevated about fivefold.

CONCLUSIONS:

Kupffer cells isolated from rats early after ethanol exhibited tolerance to LPS, whereas sensitization was observed later. It is likely that both of these phenomena are caused by gut-derived endotoxin and that sensitization in Kupffer cells is caused by increases in CD14.

PMID:
9679050
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center