Catabolism of streptokinase and polyethylene glycol-streptokinase: evidence
for transport of intact forms through the biliary system in the mouse
FH Brucato and SV Pizzo
Department of Pathology, Duke University Medical Center, Durham, NC 27710.
The catabolism of streptokinase (SK) and polyethylene glycol derivatives of
SK (PEG-SK) were studied in mice. The clearance and catabolism of
SK:plasmin (SK:Pm) and PEG-SK:Pm activator complexes were also
investigated. Native 125I-SK cleared rapidly (t1/2 = 15 minutes) from the
circulation, with the majority of the ligand accumulating in the liver and
gastrointestinal (GI) tract and a substantial fraction also localizing in
the kidneys. SK, which was removed from the plasma by the liver, was
secreted into bile and then the GI tract. Sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that 125I-SK
recovered from liver and bile was homogeneous and of the same molecular
weight (mol wt approximately 50,200) as native SK. PEG-125I-SK cleared
slowly (t1/2 greater than 200 minutes), with more than 80% of the
preparation localizing in liver and GI tract. The PEG-125I-SK secreted into
the bile was also intact. The bile containing 125I-SK was incubated with
stoichiometric amounts of plasminogen and electrophoresed under
nondenaturing conditions. This study demonstrated that the secreted SK was
able to form SK:Pg complexes. SDS-PAGE also showed activation of 125I-Pg
that was incubated with recovered bile containing the SK. 125I-SK:Pm
catabolism was also studied. In these experiments, the mol wt approximately
42,000 fragment obtained when SK is cleaved by plasmin was found in the
bile. This fragment of 125I-SK was not recovered as part of a complex with
plasmin, consistent with our previous observations that catabolism of SK:Pm
involves transfer of the plasmin to plasma proteinase inhibitors while SK
is catabolized independently. By contrast, when PEG-125I-SK:Pm was injected
into mice, only intact PEG-125I-SK was found in the bile, consistent with
our previous observations that the PEG derivatization blocks its
degradation by plasmin.
Volume 76,
Issue 1,
pp. 73-79,
07/01/1990
Copyright © 1990 by The American Society of Hematology
