Tuftsin‐macrophage interaction: Specific binding and augmentation of phagocytosis

Abstract

The binding of [3H]tuftsin to normal and in vivo stimulated mouse peritoneal macrophage populations was studied at 22 degrees C. The [3H]tuftsin binding to thioglycollate-stimulated macrophages was shown to be rapid and saturable, with an equilibrium dissociation constant (K(D)) (calculated from a Scatchard plot) of 5.3 X 10(-8) M. The calculated number of binding sites per macrophage amounts to approximately 72,000. Binding competition studies with unlabelled tuftsin yielded a K(D) of 5.0 X 10(-8) M. [3H] [N-Acetyl-Thr1]tuftsin, an inactive analog of tuftsin, failed to bind specifically to thioglycollate-stimulated macrophages. [N-Acetyl-Thr1]tuftsin and the tripeptide [Des-Arg4]tuftsin failed to compete for tuftsin binding sites, while [D-Arg4]tuftsin, an analog with small tuftsin-like activity, exhibited a low degree of inhibition of [3H]tuftsin binding. Thus a rather high degree of specificity is involved in the binding of the tetrapeptide. Normal as well as six different macrophage populations induced by stimulation with thioglycollate, concanavalin-A, starch, mineral oil, glucan and Bacillus Calmette Guerrin (BCG), exhibited a similar degree of binding of [3H]tuftsin. Corynebacterium parvum (CP)-stimulated macrophages, on the other hand, showed a 6- to 10-fold-lower capacity for tuftsin binding. Under similar experimental conditions, mouse fibroblast and lymphocyte preparations revealed no detectable specific binding. Tuftsin augmented the phagocytic response of normal and stimulated macrophages assessed both for phagocytosis mediated via the Fc-receptor and via non-specific receptors. CP-stimulated macrophages did not exhibit an increased phagocytic response upon treatment with tuftsin.

Effect of Growth Hormone-Releasing Hormone on Human Peripheral Blood Leukocyte Chemotaxis and Migration in Normal Subjects

“…It is worth noting also that other hypothalamic neuropeptides may be involved in the neural modulation of the local immune and hypersensitivity reaction [22]. Recent findings from our laboratory as well as others have shown that human monocytes are attracted towards physiologi cal concentrations of a number of neuropeptides including corticoliberin [24], substance P [ 16] and neurotensin [3]. In sum mary, these studies have provided addition support for an in volvement of GHRH in the bidirectional interaction between neuroendocrine and immune systems.…”

Integrated Communication between the Nervous, Endocrine and Immune Systems

“…Growth hormone induces T cell proliferation [ 13] and production of superoxide anions by macrophages [14], whereas thyrotropin (TSH) enhances the production of antibodies [15]. In parallel, immune cells are able to express receptors for those hormones, as for instance ACTH [16], (I-endorphin [17], growth hormone, prolactin [18], but also for other neuroendocrine peptides as vasoactive intestinal polypeptide (VIP) [19], neurotensin [20], somatostatin or substance P [21],…”

Neuropeptide Regulation of Human Thymocyte, Guinea Pig T Lymphocyte and Rat B Lymphocyte Mitogenesis

“…Accumulating evi dence indicates that neuroendocrine mechanisms can modulate this activation process [Payan and Goetzl, 1985;Wybran, 1985;Blalock and Smith, 1985;Nordlind and Mutt, 1986a, b]. Hence, studies both in vitro and in vivo, have shown that various neuropeptides influence reactions such as B lymphocyte prolifera tion and antibody synthesis, T lymphocyte prolifera tion, natural killer cell and macrophage activity as well as lymphocyte migration [Johnson et al, 1982;Bar-Shavit et al, 1982;Payan et al, 1983;Mathews et al, 1983;Ottaway, 1984;Nordlind and Mutt, 1986a, b;Sandberg and Ljungdahl, 1986]. Neuropeptides have been found in tissues where immune reactions are initiated such as the skin, gut and respiratory tract [Felten et al, 1985], Thus, in these tissues, which often are considered as primary sites of antigenic exposure, neuropeptides might be involved in the regulation of lymphocyte activation.…”