Bacterial endotoxin selectively prevents the expression of scavenger-receptor activity on human monocyte-macrophages.
Concentrations of bacterial lipopolysaccharide (LPS) as low as 1 ng/ml suppressed the activity of the scavenger receptor on cultured human monocyte-macrophages. In contrast, concentrations of LPS as high as 100 ng/ml had no effect on the activity of the low density lipoprotein (LDL) receptor. LPS and purified forms of the lipid A moiety of LPS were effective in suppressing scavenger receptor activity. However, acid hydrolysis of the labile phosphate group of the native diphosphorylated lipid A to form monophosphoryl lipid A rendered the molecule ineffective in suppressing scavenger receptor activity. LPS at a concentration of 100 ng/ml had no effect on the secretion of apolipoprotein E, phagocytic activity, tumoricidal activity, or the protein content of monocyte-macrophages. We conclude that the active component of LPS that mediates suppression of scavenger receptor activity is diphosphoryl lipid A.
Van Lenten
B J
BJ
Fogelman
A M
AM
Seager
J
J
Ribi
E
E
Haberland
M E
ME
Edwards
P A
PA
D001057:Apolipoproteins E / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D018110:Receptors, Lipoprotein
D001057:Apolipoproteins E; D004731:Endotoxins; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein