Tuftsin
Immune & Anti-InflammatoryAlso known as: Thr-Lys-Pro-Arg, TKPR, Tuftsin Tetrapeptide
Mechanism
Tuftsin is a naturally occurring four-amino-acid peptide that your body produces from IgG antibodies when they pass through the spleen. It is one of the body's primary signals for activating macrophages and other immune cells to eat and destroy pathogens (phagocytosis). People without a functioning spleen are tuftsin-deficient and more susceptible to infections. It is also the molecular ancestor of Selank — Russian scientists extended tuftsin's sequence to create Selank, one of the most popular anxiolytic peptides.
Technical detail
Tuftsin (Thr-Lys-Pro-Arg) is an endogenous tetrapeptide cleaved from the CH2 domain of the IgG heavy chain (residues 289-292) by two sequential enzymatic steps: splenic tuftsin endocarboxypeptidase removes the C-terminal Fc region, then leukokinin (a membrane-bound enzyme on neutrophils/macrophages) liberates the active tetrapeptide. Binds to specific tuftsin receptors (neuropilin-1/NRP1) on monocytes, macrophages, neutrophils, and NK cells. Activates phagocytosis, chemotaxis, and respiratory burst (superoxide production) via Fc receptor-independent mechanisms. Enhances antigen presentation by upregulating MHC class II expression. Stimulates NO production in macrophages. Modulates T-cell immunity by promoting Th1 responses. Deficiency associated with splenectomy, sickle cell disease, and certain immunodeficiencies — correlating with increased infection susceptibility. Basis for Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro), which extends tuftsin with a Pro-Gly-Pro stabilizing sequence.
Evidence
- emerging
(1991) — Elsevier BV — PMID: 10.1016/0140-6736(91)93331-3
The study found that tuftsin activity was significantly lower in patients with AIDS, AIDS-related complex (ARC), and those who had undergone splenectomy compared to healthy volunteers. Tuftsin deficiency may contribute to the risk of bacterial infection in symptomatic HIV-positive individuals.
- emerging
Congenital tuftsin deficiency.
Constantopoulos A. (1983) — Ann N Y Acad Sci. — PMID: 6201116
Case-series evidence described five pediatric patients with recurrent severe infections, absent serum tuftsin activity, otherwise normal cellular and humoral immunity, and excellent clinical response to gamma-globulin.
- moderate
Biochemical aspects of tuftsin deficiency syndrome.
Najjar VA. (1981) — Med Biol. — PMID: 6895538
Mechanistic review summarized familial tuftsin-deficiency evidence linking repeated infections to impaired phagocytosis, macrophage/granulocyte activation deficits, and loss of spleen-dependent tuftsin release pathways.