Influence of factor XIII-mediated crosslinking on fibrinolysis by leukocyte elastase

Abstract

Summary We have examined the effects of factor XIII-catalysed crosslinking of fibrin clots on their susceptibility to leukocyte proteinases in vitro. Fibrin clots from factor XIII-deficient plasma were lysed by leukocyte proteinase 2-fold faster than those from normal plasma. Similar differences in the rates of fibrinolysis between factor XIII-deficient and normal plasma clots were observed with purified leukocyte elastase. Non-crosslinked fibrin was lysed 2-fold faster than crosslinked fibrin. However, negligible differences in the rates of fibrinolysis by leukocyte proteinases and elastase were observed between crosslinked fibrin and fibrin with α 2 -plasmin inhibitor ( α 2 -PI) covalently attached. Analysis of the clots by PAGE in SDS during the elastase-induced lysis showed that α -monomer and α -polymers chains were fragmented first in both non-crosslinked and crosslinked fibrin. The non-crosslinked clots retained negligible quantities of degradation peptide fragments whereas the crosslinked clots contained significant amounts of larger molecular mass degradation fragments. These results suggest that the crosslinking of fibrin catalysed by factor XIIIa provides extended fibrin clot stability towards the leukocyte proteinases.