Neurotensin — macrophage interaction: Specific binding and augmentation of phagocytosis

Abstract

Neurotensin (NT) was found to bind to thioglycollate-elicited mouse peritoneal macrophages and to modulate their phagocytic capability. A Scatchard analysis of the binding curve of [ 3H]NT suggests the presence of two subclasses of binding sites having a.−a K D of 0.9 nM (4800 sites per cell) and b.−a K D of 28 nM (33500 sites per cell). NT as well as two of its partial sequences, NT(8–13) and NT(6–13) competed with [ 3H]NT for its binding whereas NT(1–10) was rather ineffective. [ 3H]NT was also competitively displaced by tuftsin, substance P (SP) and by SP (1–4). The K I values estimated for all the above competitive inhibitors of [ 3H]NT binding (except for NT) suggest interaction with the relatively low affinity sites. NT exerts a biphasic effect on the phagocytic response of macrophages. At a concentration range of 10 −14–10 −9 M NT had a dose dependent augmenting effect on the phagocytic response (up to 2 fold), further increase in concentration (>10 −9M) of NT resulted in a gradual decrease of the augmented response which disappears at 10 −7 M NT. NT(8–13), NT(6–13) as well as NT(1–10) augment the phagocytic response of macrophages. However the maximal effect with these peptides was attained at about 10 −7 M and stayed at the same level at concentrations up to 10 −5 M. The phagocytosis augmenting dose-response curves of these peptides resembled that of tuftsin and SP, two unrelated peptides. It is suggested that NT-phagocyte interaction may be of relevance in the regulation of the functions of phagocytic cells.