Production of macrophage-derived cytotoxic factor by N-[3-[(carbamoylmethyl)thio]propionylated] neoglycoproteins.
6-Phosphomannosylated bovine serum albumin (Man6P-BSA), a neoglycoprotein endocytosed by macrophages, bearing either 3-(2-pyridyldithio)propionyl or 3-[(carbamoylmethyl)thio]propionyl residues coming from alkylation of thiol residues by iodoacetamide were prepared and tested for their immunomodulator properties. The supernatants of mouse peritoneal macrophages incubated with Man6P-BSA bearing 3-[(carbamoylmethyl)thio]propionyl groups, and by a lesser extent 3-(2-pyridyldithio)propionyl groups, were cytotoxic to L929 cells, suggesting the presence of a tumor necrosis factor like compound. This macrophage-activation process is linked to the capacity of Man6P-BSA to be endocytosed via membrane lectins of macrophages, because the supernatants of macrophages incubated with unglycosylated conjugates were not cytotoxic. The cytotoxic activity induced by 3-[(carbamoylmethyl)thio]propionyl groups bound onto Man6P-BSA was similar to that induced by Man6P-BSA bearing muramyl dipeptide, indicating that endocytosed neoglycoproteins bearing 3-[(carbamoylmethyl)thio]propionyl residues are potent macrophage activators.
Breton
P
P
Laboratoire de Biochimie des Glycoconjugués et Lectines Endogènes, Centre de Biophysique Moléculaire CNRS, INSERM, Orléans, France.
Midoux
P
P
Petit
C
C
Bousser
M T
MT
Roche
A C
AC
Mayer
R
R
Monsigny
M
M
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000818:Animals; D002457:Cell Extracts; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D037102:Lectins / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008360:Mannosephosphates / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D011422:Propionates / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000138:chemical synthesis / Q000494:pharmacology; D013388:Succinimides; D013859:Thiocarbamates / Q000494:pharmacology
C069221:6-phosphomannosylated bovine serum albumin; D002457:Cell Extracts; D037102:Lectins; D008360:Mannosephosphates; D011422:Propionates; D013388:Succinimides; D013859:Thiocarbamates; D012710:Serum Albumin, Bovine; C018151:N-succinimidyl 3-(2-pyridyldithio)propionate; D000119:Acetylmuramyl-Alanyl-Isoglutamine