Tissue targeting and plasma clearance of cobra venom factor in mice

The tissue targeting and rate of clearance of cobra venom factor (CVF) from the circulation was studied in mice by intravenous or intraperitoneal injection of radioiodinated CVF. In both modes of administrations, CVF was targeted mainly to liver. CVF injected directly into the blood was cleared from the circulation with a plasma half life of about 10 h, whereas CVF injected into the peritoneal cavity was slowly absorbed into the blood stream reaching a maximum level at approximately 6 h, and it was then cleared from the circulation with a plasma half life of about 18 h. The rate of plasma clearance of CVF was markedly decreased upon removal of the terminal alpha-galactosyl residues of the oligosaccharide chains; the plasma half lives for intravenously and intraperitoneally administered de-alpha-galactosylated CVF were approximately 5 and approximately 10 h, respectively. However, the clearance rate was not affected by complete deglycosylation using N-glycanase or by chemical modification of the terminal galactosyl residues. Together, these data demonstrate that the terminal alpha-galactosyl residues of CVF mask the Lewis X-dependent uptake of CVF by liver.