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 intraperit oneal injection of radioiodinated CVF. In both modes of administration s, CVF was targeted mainly to liver. CVF injected directly into the bl ood was cleared from the circulation with a plasma half life of about 10 h, whereas CVF injected into the peritoneal cavity was slowly absor bed into the blood stream reaching a maximum level at similar to 6 h, and it was then cleared from the circulation with a plasma half life o f about 18 h. The rate of plasma clearance of CVF was markedly decreas ed upon removal of the terminal alpha-galactosyl residues of the oligo saccharide chains; the plasma half lives for intravenously and intrape ritoneally administered de-alpha-galactosylated CVF were similar to 5 and similar to 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 dat a demonstrate that the terminal alpha-galactosyl residues of CVF mask the Lewis X-dependent uptake of CVF by liver. (C) 1997 Academic Press.