Interactions of radiolabeled tuftsin with human neutrophils

Tuftsin, the phagocytosis-stimulating peptide, was labeled with [¹⁴C] or [¹²⁵I] at the C-terminal or N-terminal portions of the molecule and the specific interactions of the corresponding radiolabeled tuftsin with human neutrophils, lymphocytes, or monocytes were studiedin vitro. Neutrophils bound 72.2 ± 10.3%, of the¹⁴C- or¹²⁵I-labeled tuftsin in the incubation medium. When the label was incorporated at the N-terminal portion, the binding was reduced to 10%, indicating that the N-terminus is essential for the activity. Lymphocytes and monocytes also showed specific binding sites for labeled tuftsin, but the percentage binding was lower. The differences were not significant. Addition of varying amounts of unlabeled tuftsin to the labeled tuftsin-neutrophil complex, indicated quantitative competition for the binding sites on the cells. Preincubation of the neutrophils with chicken antituftsin abolished the binding.

These studies indicate that neutrophils, lymphocytes and monocytes possess receptor sites for the phagocytosis-stimulating peptide. The enzymatic cleavage and generation of tuftsin from leukokinin by the action of leukokininase on neutrophils has been suggested to be a major event in phagocytosis. The receptor sites on neutrophils for the tetrapeptide tuftsin, evidenced by our present work, provide a valuable link towards the elucidation of the mechanism of phagocytosis-stimulation. The presence of similar binding sites for tuftsin on lymphocytes and monocytes indicates a probable role for these cell populations as well, in the sequence of events during phagocytosis. Splenectomized or asplenic patients who have frequent infections may be having defective F_c receptors on these cells or these patients may be deficient in the particular subclass of IgG and/or the specific enzyme which cleaves tuftsin from it.