Enhancement of phagocytosis by neurotensin, a newly found biological activity of the neuropeptide.
Specific binding of neurotensin (NT) to mouse peritoneal thioglycollate-elicited macrophages and macrophages differentiated in vitro from bone marrow cells was demonstrated and characterized. NT binding to these phagocytes modulated their phagocytic capacity in a biphasic manner. At concentrations of 10(-14) to 10(-9) M NT, a dose-dependent augmentation of phagocytosis (up to 2-fold) was observed. Further increases in the concentration of NT resulted in a gradual decrease of the augmented response until the basal phagocytic activity (in the absence of NT) was reached. Three partial sequences of NT, NT (8-13), NT (6-13) and NT (1-10), were also effective in augmenting the phagocytic response of thioglycollate elicited macrophages, but the maximal effect was attained at about 10(-7) M and stayed at that level up to a concentration of 10(-5) M. The activity of the three NT partial sequences was comparable to that of substance P and tuftsin. Scatchard analysis of (3H)NT binding to macrophages suggested the existence of two populations of binding sites, a major population of relatively low affinity binding sites and a small population of high affinity binding sites. NT (8-13), NT (6-13), substance P and tuftsin competed with (3H)NT binding to the low affinity sites with a comparable KI to that of NT. NT (1-10) did not compete for the binding at the low affinity sites. It is suggested that NT binding to the high affinity sites leads to enhancement of phagocytosis, whereas its binding to the low affinity sites leads to inhibition of the augmented response. However, the low affinity sites are the sites of interaction of NT (8-13), NT (6-13), substance P and tuftsin with the phagocytes and their saturation with the peptides leads to augmentation of phagocytosis.
D000595:Amino Acid Sequence; D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009496:Neurotensin / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology; D014405:Tuftsin / Q000494:pharmacology
D013373:Substance P; D009496:Neurotensin; D014405:Tuftsin