Bacterial endotoxin as inhibitor of the enzymatic activity of human thrombin

European Journal of Haematology
Robert Bucki, Jennifer J Pastore

Abstract

Endotoxemia caused by bacterial lipopolysaccharides (LPS) deleteriously affects many aspects of hemostasis. Much of this effect is well characterized as being secondary to the LPS-mediated inflammatory response, but direct effects of LPS on coagulation factors may also contribute to disregulation of the hemostatic process. Spectrophotometric assays were used to investigate the effects of LPS from different bacteria on thrombin and plasmin activities. We found that enzymatic activity of purified thrombin, but not plasmin, decreases in the presence of endotoxin. LPS-mediated inhibition of thrombin activity can be reversed by plasma gelsolin and recombinant endotoxin-neutralizing protein. Preincubation of thrombin with LPS before platelet activation results in inhibition of aggregation and secretion. Additionally, a decrease of elastic shear moduli of fibrin gels was observed when their formation was induced with thrombin preincubated with LPS or when LPS was present in fibrinogen solutions during fibrin gel formation. When added to platelet-rich plasma, after activation with collagen, LPS-inhibited thrombin activity. LPS-mediated inhibition of thrombin activity may contribute to the hemostasis dysfunctions observed during endotox...Continue Reading

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Citations

Jul 7, 2009·Archivum Immunologiae Et Therapiae Experimentalis·Jennifer M SowaBennett D Elzey
Oct 21, 2009·Nanomedicine·Virginia M MillerMuthuvel Jayachandran
Jul 14, 2017·Nanomedicine·Katarzyna NiemirowiczRobert Bucki
Sep 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert BuckiPaul A Janmey

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