Regulation of nuclear antigen expression on the cell surface of human monocytes.
The expression of cell surface nuclear Ag was studied by examining the binding of anti-histone mAb to viable human peripheral blood cells. Freshly isolated cells showed no binding of these mAb. However, in vitro culture in the presence of LPS induced a dose-dependent expression of cell surface nuclear Ag on monocytes (M3+ cells). The addition of IL-1 beta to cultures also induced expression of cell surface nuclear Ag, whereas IFN-gamma was without effect. Release of nuclear material into the supernatants over time was demonstrated by using a chromatin-specific sandwich ELISA. Analysis of the DNA in the released nuclear material demonstrated banding at multiples of 190 bp, suggesting the release of polynucleosomes. Although LPS was required for cell surface nuclear Ag expression, it did not affect the release of nuclear material into the supernatants. The ability of monocytes to bind exogenous chromatin was studied by adding biotinylated-chromatin to PBL and detection with FITC-avidin. Freshly isolated PBL bound no chromatin, but when PBL were cultured in the presence of LPS, monocytes bound chromatin in a saturable manner. The LPS induction of the capacity to bind exogenous chromatin was blocked by cycloheximide. These data suggest that monocyte activation is associated with the expression of a chromatin (?nucleosome)-binding receptor and that this receptor is capable of binding nuclear material released into the cellular milieu. Monocytes may thus provide an important mechanism for the removal of extracellular nuclear material at sites of cell death and/or inflammation. The binding of nuclear Ag to cell surfaces and potential abnormalities of this binding may play a role in the induction of antinuclear antibodies and/or tissue damage in diseases such as SLE.
Emlen
W
W
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Holers
V M
VM
Arend
W P
WP
Kotzin
B
B
D034961:Antigens, Nuclear; D000954:Antigens, Surface / Q000032:analysis*; D001324:Autoantigens / Q000032:analysis*; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis*
D034961:Antigens, Nuclear; D000954:Antigens, Surface; D001324:Autoantigens; D002843:Chromatin; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D007371:Interferon-gamma