Uptake of the glycosphingolipid sulfatide in the gastrointestinal tract and pancreas in vivo and in isolated islets of Langerhans.

BACKGROUND: The glycosphingolipid sulfatide has previously been found in several mammalian tissues, but information on the uptake of exogenously administered sulfatide in different organs in vivo is limited. In pancreatic beta cells, sulfatide has been shown to be involved in insulin processing and secretion in vitro. In this study, we examined the uptake of exogenously administered sulfatide and its distribution to the pancreatic beta cells. This might encourage future studies of the function(s) of sulfatide in beta cell physiology in vivo. Radioactive sulfatide was given orally to mice whereafter the uptake of sulfatide in the gastrointestinal tract and subsequent delivery to the pancreas was examined. Sulfatide uptake in pancreas was also studied in vivo by i.p. administration of radioactive sulfatide in mice, and in vitro in isolated rat islets. Isolated tissue/islets were analysed by scintillation counting, autoradiography and thin-layer chromatography-ELISA. RESULTS: Sulfatide was taken up in the gastrointestinal tract for degradation or further transport to other organs. A selective uptake of short chain and/or hydroxylated sulfatide fatty acid isoforms was observed in the small intestine. Exogenously administered sulfatide was found in pancreas after i.p, but not after oral administration. The in vitro studies in isolated rat islets support that sulfatide, independently of its fatty acid length, is endocytosed and metabolised by pancreatic islets. CONCLUSION: Our study supports a selective uptake and/or preservation of sulfatide in the gastrointestinal tract after oral administration and with emphasises on pancreatic sulfatide uptake, i.p. administration results in sulfatide at relevant location.

Endocytosis of sulfatides by macrophages: relationship to the cellular uptake of phosphatidylserine.

These studies initially examined the effect of sulfatides on the endocytosis of phosphatidylserine (PS) liposomes in J774 macrophages employing liposomes composed entirely of PS and the nonexchangeable radiolabel [3H]cholesteryl hexadecyl ether. Bovine brain sulfatides significantly inhibited the uptake of PS liposomes by macrophages to a level of approximately 15% of control values. To examine whether macrophages were also capable of recognizing and internalizing sulfatides, sulfatide-containing liposomes were prepared using phosphatidylcholine (PC), cholesterol, and sulfatides (6:2:4 molar ratio) incorporating the same radiolabel. The sulfatide-containing liposomes were found to be avidly endocytosed by macrophages. Uptake of the sulfatide-containing liposomes by macrophages was significantly greater than the uptake of liposomes made without sulfatides. When the macrophages were incubated with the anionic compounds dextran sulfate and fucoidin, both the binding of the liposomes to the macrophages at 4 degrees C and the internalization of the liposomes at 37 degrees C were inhibited to approximately 10% of control values. The negatively charged phospholipids phosphatidylglycerol and cardiolipin significantly inhibited the uptake of sulfatide-containing liposomes, and PS was not effective in reducing the cellular uptake of these liposomes. Both oxidized low-density lipoprotein (LDL) and acetylated LDL reduced the uptake of the sulfatide-containing liposomes; the uptake observed in the presence of acetylated LDL and oxidized LDL was approximately 70% and 40%, respectively, of control values. These findings demonstrate that macrophages can efficiently endocytose both sulfatides and negatively charged phospholipids to remove them from the circulation.