Endocytosis mediated by monocyte and macrophage membrane lectins--application to antiviral drug targeting.
Sugar receptors, or membrane lectins, have been evidenced at the surface of various normal and tumour cells using fluoresceinylated neoglycoproteins (glycosylated bovine serum albumin (BSA]. By flow cytometry we have shown that macrophages bind and internalize mannosylated and 6-phosphomannosylated ligands in acidic compartments. Freshly isolated monocytes and U937, a promonocytic cell line, lack a mannose-specific receptor, but express mannose-6-phosphate (Man-6P) membrane lectin. Neoglycoproteins are potent drug carriers: muramyl dipeptide (MDP), an immunoactivator, when bound to Man-BSA or Man-6P-BSA, is 100 times more efficient than free MDP in activating macrophages; in vivo, it enables eradication of lung metastases in mice. Recently, neutral glycosylated biodegradable and nonimmunogenic polymers, were synthesized and found to be as efficient as neoglycoproteins. Antiviral drug conjugates were more active than the free drug, inhibiting the multiplication of virus (herpes) in human macrophages in vitro.
Roche
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AC
Département de Biochimie Cellulaire et Moléculaire, Centre de Biophysique Moléculaire, CNRS, Orléans, France.
Midoux
P
P
Pimpaneau
V
V
Nègre
E
E
Mayer
R
R
Monsigny
M
M
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D004705:Endocytosis; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008264:Macrophages / Q000648:ultrastructure*; D009000:Monocytes / Q000648:ultrastructure*
D000998:Antiviral Agents; D037102:Lectins