Characteristics and isolation of the phagocytosis-stimulating peptide, tuftsin

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Abstract

The phagocytosis-stimulating peptide, tuftsin, was isolated from leucokinin by digestion with the indigenous-membrane enzyme leucokininase. The enzyme was purified from blood and peritoneal polymorphonuclear neutrophils. It showed optimum activity at pH 6.8. Trypsin also releases an active peptide from leucokinin. The biological, physical and chemical properties of this peptide and that released by leucokininase are identical. The specific activities of both peptides are similar. Both enzymes, with limited treatment, release the active peptide only from the leucokinin fraction, phosphocellulose Fraction IV, of γ-globulin and only from the heavy chain. No active peptide is released by either enzyme from other Fractions I–III under similar conditions. In patients with “tuftsin-deficiency syndrome” or patients with splenectomy, no active peptide is recoverable following limited digestion by either enzyme. The biological activity of either peptide is destroyed by pronase, subtilisin, leucine aminopeptidase and carboxypeptidase B, but resists short exposure to the peptidase action of pepsin, trypsin, chymotrypsin, clostripain and papain. Chromatography on Sephadex G-10 and Aminex AG 50W-X4 showed identical elution volumes. On silica gel G both peptides, free or dansylated, yielded identical RF values in several solvents.

The peptide has been isolated from phosphocellulose Fraction IV as well as from unfractionated γ-globulin. Sequence analysis yielded Thr-Lys-Pro-Arg.

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