A possible role for mono(ADP-ribosyl)transferase in the signalling pathway mediating neutrophil chemotaxis

1 Mono(ADP-ribosyl)transferase activity has been identified on the external surface of human polymorphonuclear neutrophil leucocytes (PMNs). The enzyme is released from the plasma membrane by phosphoinositide-specific phospholipase C, suggesting a glycosylphosphatidylinositol (GPI) linkage of the enzyme to the plasma membrane. Partial sequence of cDNA encoding the enzyme suggests that it is identical to the GPI-linked mono(ADP-ribosyl)transferase identified previously on human skeletal muscle.
2 A panel of inhibitors of mono(ADP-ribosyl)transferase (including vitamins K₁ and K₃, novobiocin and nicotinamide) showed a rank order of inhibitory potency similar to that described for other mono(ADP-ribosyl)transferases. Furthermore, the mono(ADP-ribosyl)ation of agmatine was inhibited also by diethylamino(benzylidineamino)guanidine (DEA-BAG), another substrate of the enzyme related structurally to arginine.
3 There was a close linear correlation between the I C ₅₀ values for inhibition of mono(ADP-ribosyl)ation of agmatine by DEA-BAG or the enzyme inhibitors and their I C ₅₀ values for inhibition of receptor-dependent polymerization of cytoskeletal actin and chemotaxis.
4 These results suggest a role for mono(ADP-ribosyl)transferase in the transduction pathway involved in receptor-dependent re-alignment of the cytoskeleton during neutrophil chemotaxis.