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Etude de l'impact des polynucléaires neutrophiles et de deux enzymes dérivées, cathepsine G et élastase sur la coagulation

Abstract : Polymorphonuclear neutrophils (PMN) are the most abundant nucleated cells in blood. Their involvement in haemostasis - in particular in coagulation and clot formation - is not a new concept, but is not yet fully understood. Many data from the literature indicate that these cells can enhance (even trigger) coagulation, whereas others indicate it can impair fibrin formation and facilitate clot elimination. Among the hypotheses explaining this involvement, attention has focused on PMN granules enzymes, in particular, Cathepsin G (Cath G) and elastase (HNE). We first aim at studying in healthy subjects the impact of PMN as well as Cath G and HNE on coagulation by use of global tests: rotative thromboelastometry (ROTEM®) and thrombin generation test (CAT®). Second, procoagulant potential of PMN is investigated using CAT® in patients affected by myeloproliferative disorders (MPD), with presence of JAK2V617F mutation. Under our conditions, PMN show an unambiguous procoagulant activity, inducing systematically a decrease in clotting time, along with an increase in total thrombin work. This activity is proportional with PMN concentration; fMLP-induced PMN stimulation enhances also it, but this is not related to tissue factor activity. Both Cath G and HNE induce a decrease in clotting time, but support procoagulant (by inactivation of inhibitors such as TFPI) as well as anticoagulant activity (by inactivation of factor V or fibrin(ogen) degradation). At last, data obtained don't show MPD-associated hypercoagulability which can be attributed to PMN.
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https://hal.univ-lorraine.fr/tel-01748317
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Julien Perrin. Etude de l'impact des polynucléaires neutrophiles et de deux enzymes dérivées, cathepsine G et élastase sur la coagulation. Biologie cellulaire. Université Henri Poincaré - Nancy 1, 2009. Français. ⟨NNT : 2009NAN10107⟩. ⟨tel-01748317⟩

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