Decay-accelerating factor functions as a signal transducing molecule for human monocytes.
Decay-accelerating factor (DAF) is a glycosylphosphatidylinositol-anchored membrane protein that protects cells from damage by autologous complement activation. Of the four mAb against DAF prepared in our laboratory, 1C6 completely blocked DAF function, whereas 5B2 partially blocked it. Using these mAb, we investigated whether human monocytes were activated via DAF molecules. When monocytes were incubated with 1C6 alone, glucose was consumed in significant amounts and phagocytosis of latex beads was enhanced, indicating that the monocytes had been activated. However, 1C6 did not enhance the production of monokines, TNF-alpha, and IL-1 alpha and -beta. The F(ab')2 fragment of 1C6 also activated monocytes, whereas 5B2 and the Fab fragment of 1C6 could not. To further examine monocyte activation, these cells were treated with phosphatidylinositol-specific phospholipase C. Increased glucose consumption and enhanced phagocytic activity by 1C6 were considerably reduced in monocytes treated with phosphatidylinositol-specific phospholipase C. In addition, we found that 1C6 stimulated the generation of inositol trisphosphate. These results demonstrate that the signal transmitted via the DAF molecule is capable of stimulating monocytes.
Shibuya
K
K
Institute of Clinical Medicine, University of Tsukuba, Japan.
Abe
T
T
Fujita
T
T
D000911:Antibodies, Monoclonal / Q000276:immunology; D018958:CD55 Antigens; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008565:Membrane Proteins / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism*; D010587:Phagocytosis; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018958:CD55 Antigens; D008565:Membrane Proteins; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium