The effect of Tuftsin on the nitrous blue tetrazolium reduction of normal human polymorphonuclear leukocytes.

Abstract

A B S T R A C T The influence of Tuftsin, the synthetic phagocytosis-stimulating tetrapeptide (L-threonyl-L-lysyl-L-prolyl-L-arginine), on the nitrous blue tetrazolium (NBT) reduction by human polymorphonuclear leukocytes was investigated. It was found that this substance increases the NBT reduction by approximately as much as endotoxin. Other tetrapeptides do not share this property. When Tuftsin analogs are added to the cell suspension and incubated, they prevent the action of both Tuftsin and endotoxin but not of methylene blue. When washed of the analogs, the cells regain the property to be activated by both Tuftsin and endotoxin. It appears that methylene blue on one hand and Tuftsin and endotoxin on the other hand have different sites for their actions. We suggest that whereas methylene blue diffuses into the cell and acts directly upon the hexosemonophosphate shunt activation, Tuftsin and endotoxin appear to act on the cell membrane binding to specific receptors. By treating the cells with Tuftsin analogs, we probably block these receptors.

Anti-tumour effect of the physiological tetrapeptide, tuftsin

“…In addition to human and dog PMNs, tuftsin has been shown to stimulate the phagocytic activity of guinea-pig peritoneal granulocytes, mouse peritoneal macrophages, and rabbit alveolar macrophages (Constantopoulos & Najjar, 1972). Tuftsin also enhances the reduction of nitrous blue tetrazolium by human PMNs (Spirer et al, 1975;Fridkin et al, 1977), the random migration of human mononuclear cells (Nishioka, 1976(Nishioka, , 1978 and antigen-specific macrophagedependent education of T lymphocytes (Tzehoval et al, 1978). Recently, the presence of specific binding sites for tuftsin on human PMNs and monocytes has also been revealed .…”

“…The peptide, whose sequence has been determined as Thr-Lys-Pro-Arg (Nishioka et al, 1972(Nishioka et al, , 1973a, has been chemically synthesized by various investigators (Nishioka et al, 1972(Nishioka et al, , 1973bSpirer et al, 1975;Yajima et al, 1975;Okamoto & Shimamura, 1976;Konopinska et al, 1977;Fridkin et al, 1977). The physiological significance of tuftsin has been demonstrated in splenectomized dogs and humans (Najjar & Constantopoulos, 1972; Constantopoulos et al, 1 973a; Spirer et al, 1977a, b) and also in patients with acute myelocytic leukemia (Constantopoulos et al, 1973b) whose low levels of serum tuftsin coincide with a high incidence of infections.…”

Molecular Basis of Familial and Acquired Phagocytosis Deficiency Involving the Tetrapeptide, Thr-Lys-Pro-Arg, Tuftsin

“…Some of these have been described [6,7,24], The methods we used at the time for diagonosis were tedious and required specialized equipment and personnel. However, recently F r id k in , S pir e r and their colleagues have devised simpler and precise immunochemical procedures for assaying tuftsin in quantitative terms [15,16,32,33].…”

“…In vitro tests employed various target particles; latex particles, yeast cells [15,16], staphylococci [5,14] and 116 N ajjar nitro-blue tétrazolium [32,33], The high specific activity observed with staphylococci was also confirmed with yeast cells. In each case, half maximal activation was obtained in our laboratory and in F r id k in 's at 2 x 10'7 M [5,15] and a major stimulation was obtained at half that concen tration [15].…”

Klinische und physiologische aspekte von Tuftsin-Mangelsyndromen mit gest�rter Phagocytose

“…It is certainly true that such cases are not subject to overwhelming infections as occurs following elective splenectomy [10][11][12]19]. [45]. In cases of deficiency the reduced dye formed is greatly diminished compared to normals [45].…”