May 16, 2016

Acute induction of anomalous blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide (LPS)

BioRxiv : the Preprint Server for Biology
Etheresia PretoriusDouglas B Kell

Abstract

It is well known that a variety of inflammatory diseases are accompanied by hypercoagulability, and a number of more-or-less longer-term signalling pathways have been shown to be involved. In recent work, we have suggested a direct and primary role for bacterial lipopolysaccharide in this hypercoagulability, but it seems never to have been tested directly. Here we show that the addition of tiny concentrations (0.2 ng.L-1) of bacterial lipopolysaccharide (LPS) to both whole blood and platelet-poor plasma of normal, healthy donors leads to marked changes in the nature of the fibrin fibres so formed, as observed by ultrastructural and fluorescence microscopy (the latter implying that the fibrin is actually in an amyloid β-sheet-rich form. They resemble those seen in a number of inflammatory (and also amyloid) diseases, consistent with an involvement of LPS in their aetiology. These changes are mirrored by changes in their viscoelastic properties as measured by thromboelastography. Since the terminal stages of coagulation involve the polymerisation of fibrinogen into fibrin fibres, we tested whether LPS would bind to fibrinogen directly. We demonstrated this using isothermal calorimetry. Finally, we show that these changes in fibre...Continue Reading

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Mentioned in this Paper

Biochemical Pathway
Fibrin Measurement
Thrombophilia
APP protein, human
Whole Blood
Fibrinogen
Fibrinogen Assay
F2 gene
Inflammatory Disorder
Thrombin

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