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Accueil > Publications > Recherche par années > Années 1990 > 1991

Breton, P ; Midoux, P ; Petit, C ; Bousser, MT ; Roche, AC ; Mayer, R ; Monsigny, M

Production of macrophage-derived cytotoxic factor by n-[3-[(carbamoylmethyl)thio]propionylated] neoglycoproteins

Bioconjugate Chemistry 2 (1) 16-18

par Administrateur - publié le

Abstract :

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.