Distinctive immunomodulating properties and interactivity with model membranes and cells of two homologous muramyl dipeptide derivatives differing by their lipophilicity.
We have studied and compared the immunomodulating activities of two muramyl dipeptide (MDP) derivatives: beta-heptylglycoside-MDP (C7H15MDP) and beta-hexadecylglycoside-MDP (C16H33MDP). The amphiphilic derivative C7H15MDP has been found to be a more effective stimulator of T lymphocyte proliferation and allospecific cytotoxic T cell generation in a mixed lymphocyte culture, and a more effective activator of interleukin-1 (IL-1) and tumour necrosis factor (TNF) production by murine peritoneal macrophages, in comparison with MDP and C16H33MDP used in equimolar concentrations. C7H15MDP also stimulated cytotoxicity of natural killer (NK) cells: On the contrary, its lipophilic homologue C16H33MDP did not show such activities in vitro except for its influence on IL-1 and TNF production. We have found significant differences in the interaction of these two 14C-labelled MDP derivatives with model membranes and in the uptake of these preparations by erythroleukemia K562 cells. We consider the hydrolipophilic balance of the above preparations to be the main cause of their different interactions with membranes and their uptake by cells and, as a result, their opposite immunomodulating activities in vitro.
Kalyuzhin
O V
OV
Laboratory of Cellular Immunopathology and Biotechnology, Russian Academy of Medical Sciences, Moscow, Russia. root@strip.msk.ru
Zemlyakov
A E
AE
Fuchs
B B
BB
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000502:physiology; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D008567:Membranes, Artificial; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine