Background: Proteases of the blood coagulation, thrombin and activated protein C (APC) are involved in the development of inflammatory processes. Diabetes mellitus (DM) is characterized by a high glucose in blood, a hyperglycemia. It contributes to vascular damage and leads to the development of DM complications such as neuropathy, angiopathy, diabetic foot and others. The understanding of the mechanism of haemostasis proteases involvement in the inflammation accompanied many diseases is one of the fundamental problems of physiology.
Aims: The aim of this study to investigate the features of thrombin and APC-induced regulation of mast cell and macrophage(MP) activity in diabetes, inflammation and high glucose.
Methods: Peritoneal mast cells and MP isolated from rat with streptozotocin-induced DM, thioglycolate-induced inflammation and RBL-2H3 were analyzed. The evaluation of proliferation and accumulation of nitrites, intracellular calcium, secretion and actin cytoskeleton were performed for comparing effects of thrombin and APC on cells.
Results: At the first time has been shown that the effect of thrombin on mast cell secretion is dose-dependent in both experimental diabetes and inflammation. It has been shown that high glucose and DM reduce baseline proliferation and the production of NO by MP. Proinflammatory activity of MP is potentiated by hyperglycemia, one of the main pathological factors of diabetes. A high glucose impacts proliferation and NO production and increases the thrombin and APC-induced effects on cells. The PKC activator – phorbol ester abolished the pro-inflammatory effect of thrombin, that indicates the involvement of PKC in protease effects.
Conclusions: Thus, this study points to the leading role of glucose in the regulation of MP and mast cells activation. In contrast to inflammation, diabetes is a more significant factor that changes the effect of protease on mast cells, probably due to a change in the affinity of the PAR-1 receptor.
This work was supported by RFBR 19-015-00529.
To cite this abstract in AMA style:Gorbacheva L, Kiseleva E, Goliako I. Diabetes Mellitus Increases Thrombin and Activated Protein C Effects on Mast Cell and Macrophages [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/diabetes-mellitus-increases-thrombin-and-activated-protein-c-effects-on-mast-cell-and-macrophages/. Accessed November 26, 2020.
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