Accession Number:

ADA160439

Title:

Prostanoid Production by Lipopolysaccharide-Stimulated Kupffer Cells

Descriptive Note:

Scientific rept.

Corporate Author:

ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD

Report Date:

1985-05-01

Pagination or Media Count:

8.0

Abstract:

Although some data suggests that macrophages in the reticuloendothelial system RES are important sources of thromboxane A2 TxA2 and prostacyclin PGI2 during endotoxic shock, we are unaware of data documenting the ability of hepatic macrophages Kupffer cells to release either TxA2 or PGI2 when exposed to lipopolysaccharide endotoxin, LPS. In this study, Kupffer cells were examined for their ability to release prostaglandin E2 PGE2 , TxA2, and PGI2 following stimulation with 0, 1.0, 50.0, and 100.0 micrograms ml of Escherichia coli LPS. Kupffer cells were obtained from rat livers by enzymatic digestion with 0.05 collagenase followed by enrichment of the macrophage population on the basis of differences in density and adherence among the various cell populations isolated. Based on several criteria phagocytosis of opsonized sheep erthrocytes, positive staining for esterase and peroxidase, failure to replicate, 95 of adherent cells were Kupffer cells. After 4 days of incubation, cells were stimulated with various doses of LPS for 4 and 8 hr. Prostanoid concentrations in culture supernatants were determined by radioimmunoassay. Increasing doses of LPS significantly P 0.0001 increased the concentration of immunoreactive PGE2 iPGE2 and iTxB2 the stable metabolite of TxA2. The concentration of i6-keto-PFG1a stable metabolite of PGI2 increased following stimulation with 1.0 microgramsml of LPS, but declined as the dose of LPS was increased. The results provide evidence that endotoxin-activated Kupffer cells, like other macrophage populations, release several metabolites of arachidonic acid.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE