In vivo immunopharmacological properties of tuftsin (Thr-Lys-Pro-Arg) and some analogues.
Tuftsin (Thr-Lys-Pro-Arg) is part of the Fc fragment of a leukophilic IgG and is a stimulator of the phagocytic activity of macrophages and polymorphonuclear cells (PMN) when cleaved from its carrier molecule. Tuftsin was shown to stimulate in vitro all PMN and macrophage functions examined through binding to specific cell surface receptors. In the present work, we provide further evidence that synthetic tuftsin administered to mice may act as an immunomodulator and that its effects on immune functions may result from a primary action on macrophages. After i.v. injection at a dosage of 25 micrograms/mouse, tuftsin stimulated effector (phagocytosis) and regulatory (IL1 production) functions of macrophages and potentiated DTH reaction. Lymphocyte functions (proliferative response to mitogens, T cell-mediated cytotoxicity, IL2 and gamma IFN production) were depressed at times at which macrophage activities were maximally enhanced, suggesting that negative regulatory functions of these latter cells were also stimulated. Tuftsin analogues were synthetized representing substitution or derivatization of the threonyl residue. The relative potencies of these analogues in augmenting phagocytosis-induced chemiluminescence of macrophages were tuftsin greater than or equal to (Gly1)-tuftsin greater than for-tuftsin greater than (for-Met1)-tuftsin greater than (Met1)-tuftsin. Concerning potentiation of DTH reaction the order was (Gly1)-tuftsin greater than or equal to (for-Met1)tuftsin greater than tuftsin greater than (Met1)-tuftsin greater than for-tuftsin. In contrast to tuftsin, none of the analogues induced depression of spleen cell reactivity to mitogens. In addition, (for Met1)-tuftsin administration resulted in an increased production of IL2 and IFN by ConA-stimulated spleen cells.(ABSTRACT TRUNCATED AT 250 WORDS)
I
I
Florentin
V
V
Chung
J
J
Martinez
J
J
Maral
Y
Y
Le Garrec
G
G
Mathé
D000276:Adjuvants, Immunologic; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007372:Interferons / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects; D008163:Luminescent Measurements; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology; D014405:Tuftsin / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D007376:Interleukin-2; D007372:Interferons; D014405:Tuftsin