Tuftsin, a natural activator of phagocyte cells: an overview.
The recognition that a small oligopeptide was responsible for the full stimulation effect of specific cytophilic gamma-globulin on blood neutrophils arose from a study of the kinetics of phagocytosis. These were unusual in that the stimulation was short lived and that preincubation of the phagocyte with the gamma-globulin rendered the latter inactive. The oligopeptide was isolated, its structure determined (Thr-Lys-Pro-Arg) and synthesized. The discovery of human mutants with tuftsin deficiency exhibiting signs and symptoms of frequent severe infection further emphasized the specific biological function of the tetrapeptide. The mutant peptide was isolated, sequenced (Thr-Glu-Pro-Arg), and synthesized. Further studies showed that tuftsin requires two enzymes for its liberation from the parent carrier gamma-globulin. One enzyme is in the spleen that cleaves distal to the arginine end, and the other, on the outer side of the plasma membrane, cleaves proximal to the threonine residue. The tetrapeptide tuftsin stimulates all functions of phagocytic cells: phagocytosis, pinocytosis, motility, immunogenic activity including processing of the antigen and augmentation of the number of antibody-forming cells, bactericidal activity, and, above all, tumoricidal activity. The latter has been shown by several laboratories.
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents; D001770:Blood Bactericidal Activity; D043424:Carboxypeptidase B; D002268:Carboxypeptidases / Q000494:pharmacology; D002352:Carrier Proteins; D002462:Cell Membrane / Q000201:enzymology; D002465:Cell Movement; D010450:Endopeptidases / Q000494:pharmacology; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010447:Peptide Hydrolases; D010586:Phagocytes / Q000502:physiology*; D013154:Spleen / Q000201:enzymology; D014405:Tuftsin / Q000031:analogs & derivatives / Q000172:deficiency / Q000276:immunology / Q000502:physiology*
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D002268:Carboxypeptidases; D010450:Endopeptidases; D010447:Peptide Hydrolases; C002128:leucokininase; D043424:Carboxypeptidase B; D014405:Tuftsin