Role of the macrophage galactose lectin in the uptake of desialylated LDL.
Desialylated low density lipoprotein (LDL) is rapidly taken up and accumulated by both peripheral blood monocytes and cells isolated from human arterial intima consisting predominantly of smooth muscle cells. It is shown that thioglycollate (TG)-elicited mouse macrophages and mouse peritoneal macrophages stimulated with lipopolysaccharide (LPS) show increased expression of a membrane-bound, galactose-specific lectin that could be responsible for this uptake. In LPS-stimulated macrophages accumulation of desialylated LDL is increased ca. 2.6-fold. Accumulation of acetylated LDL in the same cells is reduced, suggesting that the galactose-specific lectin might be responsible for the uptake of desialylated LDL. Transfection of cells with the mouse macrophage Gal/GalNAc-specific lectin (MMGL) increased their capacity to take up asialofetuin (ASF) and, to a smaller extent, desialylated LDL. The uptake of desialylated LDL was small, most likely due to the high k(d) of MMGL for biantennary oligosaccharides as found on LDL, and low concentration of LDL achieved in tissue culture experiments. The data suggest that the expression of galactose-specific lectins can be elevated under inflammatory conditions, and that these receptors could contribute to foam cell formation under conditions of high desialylated LDL concentration, as might be found in arterial intima.
Bartlett
A L
AL
Centre for Immunology, University of NSW and St Vincent's Hospital, Darlinghurst, NSW 2010, Sydney, Australia.
Grewal
T
T
De Angelis
E
E
Myers
S
S
Stanley
K K
KK
D000818:Animals; D001212:Asialoglycoproteins / Q000493:pharmacokinetics; D002352:Carrier Proteins / Q000494:pharmacology; D002460:Cell Line; D060748:Fetuins; D019084:Fluorescent Antibody Technique, Indirect; D005690:Galactose / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000493:pharmacokinetics*; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D013864:Thioglycolates / Q000494:pharmacology; D014162:Transfection; D000509:alpha-Fetoproteins / Q000493:pharmacokinetics
D001212:Asialoglycoproteins; D002352:Carrier Proteins; C064720:Clec10a protein, mouse; D060748:Fetuins; D037102:Lectins; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D013864:Thioglycolates; C032629:acetyl-LDL; D000509:alpha-Fetoproteins; C017029:asialofetuin; D019158:N-Acetylneuraminic Acid; D005690:Galactose