A POSSIBLE ROLE FOR MONO(ADP-RIBOSYL)TRANSFERASE IN THE SIGNALING PATHWAY MEDIATING NEUTROPHIL CHEMOTAXIS

1 Mono(ADP-ribosyl) transferase activity has been identified on the ex ternal surface of human polymorphonuclear neutrophil leucocytes (PMNs) . The enzyme is released from the plasma membrane by phosphoinositide- specific phospholipase C, suggesting a glycosylphosphatidylinositol (G PI) linkage of the enzyme to the plasma membrane. Partial sequence of cDNA encoding the enzyme suggests that it is identical to the GPI-link ed mono(ADP-ribosyl)transferase identified previously on human skeleta l muscle. 2 A panel of inhibitors of mono (ADP-ribosyl)transferase (in cluding vitamins K-1 and K-3, novobiocin and nicotinamide) showed a ra nk order of inhibitory potency similar to that described for other mon o(ADP-ribosyl) transferases. Furthermore, the mono(ADP-ribosyl)ation o f agmatine was inhibited also by diethylamino (benzylidineamino) guani dine (DEA-BAG), another substrate of the enzyme related structurally t o arginine. 3 There was a close linear correlation between the IC50 va lues for inhibition of mono(ADP-ribosyl) ation of agmatine by DEA-BAG or the enzyme inhibitors and their IC50 values for inhibition of recep tor-dependent polymerization of cytoskeletal actin and chemotaxis. 4 T hese results suggest a role for mono(ADP-ribosyl) transferase in the t ransduction pathway involved in receptor-dependent re-alignment of the cytoskeleton during neutrophil chemotaxis.