ADP-ribosylation of tuftsin suppresses its receptor-binding capacity and phagocytosis-stimulating activity to murine peritoneal macrophages.

Arginine-specific ADP-ribosyltransferase present in granules of chicken polymorphonuclear leukocytes (so-called heterophils) is released into the extracellular space by stimulus of calcium ionophore A23187 or opsonized zymosan [Terashima et al. (1996) J. Biochem. 120, 1209-1215]. In the present work, we examined extracellular targets of the released transferase and identified tuftsin, a phagocytosis-stimulating tetrapeptide derived from leukokinin, as a preferential substrate of the enzyme in chicken plasma. Specific binding of FITC-tuftsin to murine peritoneal macrophages, observed under a fluorescent microscope, was impaired by ADP-ribosylation of the labelled peptide. Phagocytic assay analyzed by flow cytometry revealed that ADP-ribosylation of tuftsin decreased its phagocytosis-stimulating activity towards the macrophages. Thus, the ADP-ribosylation of tuftsin apparently decreases its biological activity and ADP-ribosylation may possibly be involved in inflammatory processes through alterations in tuftsin activity.