Enhanced expression of the complement-regulatory factor C8 binding protein (C8bp) on U937 cells after stimulation with IL-1 beta, endotoxin, IFN-gamma, or phorbol ester.
C8 binding protein (C8bp) is a 65-kDa membrane glycoprotein that inhibits complement-mediated lysis by homologous C5b-9. C8bp was first identified on human erythrocytes, but could also be detected on peripheral blood cells, platelets, glomerular cells and synovial fibroblasts. Lack of C8bp as seen in patients with paroxysmal nocturnal hemoglobinuria type III results in enhanced susceptibility of the cells toward C5b-9. We studied C8bp expression on the promonocytic cell line U937. In addition to the membrane-bound C8bp, a cytoplasmic form of C8bp could also be identified by immunofluorescence, blotting, and precipitation. Stimulation of the cells with IL-1 beta, endotoxin, IFN-gamma, or phorbol ester increased C8bp surface expression. Because cycloheximide did not inhibit enhanced surface expression, it was most probably mobilized from cytoplasmic reservoirs. Thus, resistance of nuclear cells to complement attack seems to be based on two events: 1) the removal of the C5b-9 complex from the membrane; and 2) expression of regulatory surface proteins such as C8bp, which inhibit C5b-9-mediated lysis. We propose that the C8bp mobilization by cytokines might provide an additional protection against complement attack by its known interference with the C5b-9 assembly.
Schieren
G
G
Institute of Immunology, University of Heidelberg, Federal Republic of Germany.
Janssen
O
O
Hänsch
G M
GM
D001798:Blood Proteins / Q000032:analysis* / Q000502:physiology; D018957:CD59 Antigens; D002352:Carrier Proteins / Q000032:analysis* / Q000502:physiology; D002460:Cell Line; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003165:Complement System Proteins / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000032:analysis*; D011951:Receptors, Complement / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D001798:Blood Proteins; D018957:CD59 Antigens; D002352:Carrier Proteins; D015938:Complement Membrane Attack Complex; D004731:Endotoxins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C051590:CD59 protein, human; D007371:Interferon-gamma; D003165:Complement System Proteins; D013755:Tetradecanoylphorbol Acetate