Macrophage activation by muramyl dipeptide bound to neoglycoproteins and glycosylated polymers: cytotoxic factor production.
Some biological functions of macrophages can be stimulated by muramyl dipeptide (MDP) in vitro. Such stimulation is more efficient when MDP is bound to macromolecule carriers. The macrophage stimulation by MDP bound to glycosylated serum albumin (BSA) or bound to gluconoylated and glycosylated poly-L-lysine (PLK) is investigated. These two types of MDP conjugates are more efficient than free MDP in rendering mouse peritoneal and rat alveolar macrophages cytostatic against various tumor cells. However, the release of mitogenic factor or cytotoxic factor (CF) by activated macrophages varies according to the nature of the carrier (BSA or PLK) and to the nature and content of sugar residues bound to the macromolecule carrier (mannose or 6-phosphomannose). Macrophages activated by MDP bound to glycosylated BSA release mitogenic factor and CF into the medium; anti-recombinant tumor necrosis factor (rTNF) totally inhibits the cytotoxicity of the supernatant. On the contrary, MDP bound to glycosylated PLK induces no secretion of mitogenic factor and a very small amount of CF in the culture medium. The role of CF in the cytostatic activity of activated macrophages is discussed. The released CF is not involved in the cytostatic activity, but TNF-like molecules, expressed at the membrane level, could be implied because anti-rTNF abrogates 40% of the cytostatic activity of the macrophages.
Petit
C
C
Département de Biochimie, Centre de Biophysique Moléculaire, C.N.R.S., Orléans, France.
Monsigny
M
M
Roche
A C
AC
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003603:Cytotoxins / Q000096:biosynthesis*; D004337:Drug Carriers; D006001:Glycoconjugates; D006023:Glycoproteins; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D011108:Polymers; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D003603:Cytotoxins; D004337:Drug Carriers; D006001:Glycoconjugates; D006023:Glycoproteins; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine