Polytuftsin: its possible effects and mechanism during macrophage activation.
Polytuftsin (PT) a 35-40 repeat unit of tuftsin (TKPR), when administered as a conjugate with the malarial peptide, ring-infected erythrocyte surface antigen (RESA), enhanced antigen-induced lymphoproliferation and antibody levels in mice as compared to RESA alone. This enhancement was unrelated to the H-2 background of the animals. The present study was undertaken with a view to understanding the mechanism(s) responsible for this immune enhancement. Peritoneal adherent cells (PAC) from H-2b and H-2d mice were incubated with RESA alone, PT-conjugated RESA, a physical mixture of RESA + PT and PT alone. They were subsequently evaluated for I-A expression using monoclonal antibodies and flow cytometry as well as cell-ELISA. Significant increase in I-A expression on PAC was observed in all 4 groups as compared to untreated cells. Whereas cells treated with PT-conjugated RESA showed highly significant increase in I-A (P < 0.001), the other groups showed moderate increase (P < 0.05). This enhancement was attributable to increase in the number of I-A-positive cells rather than I-A molecules per cell. Moreover, IL-1 release, as assayed by bioassay, was significantly higher in cells treated with conjugated RESA as compared to cells treated with RESA or PT alone (P < 0.05). Thus, it would appear that PT-conjugated RESA peptide of the malarial antigen selectively enhances major histocompatibility complex (MHC) class II molecules on antigen-presenting cells (APC) and may therefore improve immune functions by stimulating better antigen presentation and proliferation of T cells.
Dhawan
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Department of Biochemistry, All India Institute of Medical Sciences, New Delhi.
Nath
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Rao
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology; D011108:Polymers / Q000378:metabolism / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000494:pharmacology; D014405:Tuftsin / Q000378:metabolism / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D011108:Polymers; D015800:Protozoan Proteins; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum; C053968:polytuftsin; D014405:Tuftsin