1887

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Volume 52, Issue 8

Binding of enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells Free

Abstract

Infection by the human opportunistic fungal pathogen has been increasing over recent years. In an attempt to understand the molecular mechanism of invasion across host tissues, the relationship of enolase to human plasminogen/plasmin was investigated. enolase is a cell-surface protein and an immunodominant antigen in infected patients’ sera. Plasminogen is an abundant plasma protein. Several lines of evidence support the binding of enolase to human plasminogen. Firstly, it was found that various strains were able to bind to plasminogen and its active form, plasmin. Secondly, recombinant enolase was retained in a nickel-chelating affinity column matrix that can bind I-labelled plasminogen or plasmin in a dose-dependent manner. Plasmin(ogen)-specific inhibitors, such as ε-aminocaproic acid and aprotinin, can effectively block plasmin-binding activity. Thirdly, as with many plasminogen receptors, binding of enolase to plasmin(ogen) is lysine-dependent, whereas little inhibition occurred with arginine, aspartate and glutamate. Fourthly, immobilized enolase enhanced plasminogen's affinity for streptokinase at least tenfold, as demonstrated by its activation of plasmin activity. To elucidate the biological significance of this result, it was demonstrated that the plasmin(ogen)-bound cells were able to induce fibrinolysis activity in a matrix-gel assay. Furthermore, plasmin-bound cells had an increased ability to cross an blood–brain barrier system. The results given here indicate that enolase is a plasminogen- and plasmin-binding protein and that the interaction of enolase with the plasminogen system may contribute to invasion of the tissue barrier.

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2003-08-01
2024-04-19
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Binding of Candida albicans enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells
J. Med. Microbiol. 52, 615 (2003); https://doi.org/10.1099/jmm.0.05060-0
/content/journal/jmm/10.1099/jmm.0.05060-0
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