Lipopolysaccharide-induced inhibition of scavenger receptor expression in human monocyte-macrophages is mediated through tumor necrosis factor-alpha.
The exposure of mononuclear cells to LPS results in a variety of cellular alterations including changes in the expression of various membrane receptors. In human monocyte-macrophages the development of the scavenger receptor, which mediates the uptake and internalization of chemically modified proteins, was suppressed by 100 ng/ml of LPS, concomitant with a reduction in receptor mRNA. Removal of LPS from the media resulted in a rapid increase in scavenger-receptor activity and mRNA that was further enhanced by macrophage-CSF and granulocyte/macrophage-CSF. However, neither macrophage-CSF nor granulocyte/macrophage-CSF could overcome the suppression of scavenger-receptor activity in the presence of LPS. The LPS-induced suppression of the scavenger receptor could be overcome by the co-addition of neutralizing antibody to TNF-alpha. TNF-alpha added to human monocyte-macrophages in the absence of LPS suppressed scavenger receptor activity to the same extent as did LPS. In contrast, the co-addition of LPS and neutralizing antibodies to either IFN-gamma or to IL-1 beta did not overcome the inhibitory effects of LPS on scavenger receptor activity. We conclude that the LPS-induced suppression of the scavenger receptor is mediated primarily through TNF-alpha.
van Lenten
B J
BJ
Department of Medicine, University of California, School of Medicine, Los Angeles 90024-1679.
Fogelman
A M
AM
D001483:Base Sequence; D015152:Blotting, Northern; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D015345:Oligonucleotide Probes / Q000737:chemistry; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D015345:Oligonucleotide Probes; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor