Contribution of endothelial cell and macrophage activation in the alterations induced by the venom of Micrurus tener tener in C57BL/6 mice. (December 2019)

• Record Type: Journal Article
• Authors: Salazar, Emelyn; Salazar, Ana María; Taylor, Peter; Urdanibia, Izaskun; Pérez, Karin; Rodríguez-Acosta, Alexis; Sánchez, Elda E.; Guerrero, Belsy
• Is Part Of: Molecular immunology. Volume 116(2019:Dec.)
• Page Start: 45
• Page End: 55
• Publication Date: 2019-12
• Subjects: 3FTX 3 finger toxins -- aPTT activated partial thromboplastin time -- CAM cell adhesion molecules -- CD62E E-selectin -- FBS fetal bovine serum -- FVIIa factor VII activated -- FX factor X -- FXa factor X activated -- ICAM-1 intercellular adhesion molecule 1 -- IL-1 interleuquin 1 -- IL-6 interleuquin 6 -- IL-8 interleuquin 8 -- LC50 lethal concentration 50 -- LPS lipopolysaccharide -- LSEC liver sinusoidal endothelial cell -- Mtt Micrurus tener tener -- NO nitric oxide -- NO2− nitrites -- NO3− nitrates -- PAI-1 plasminogen activator inhibitor-1 -- PAR-2 protease activated receptor-2 -- PBS phosphate-buffered saline -- PLA2 phospholipases A2 -- PT prothrombin time -- SRB sulphorhodamine B -- SVMP snake venom metalloproteinases -- TF tissue factor -- TFPI tissue factor pathway inhibitor -- TG thioglycollate -- Th thrombin -- TNF-α tumor necrosis factor-α -- tPA tissue plasminogen activator -- uPA urokinase plasminogen activator -- uPAR urokinase plasminogen activator receptor -- VCAM-1 vascular cell adhesion protein 1 -- vWF von Willebrand Factor; Micrurus tener tener -- Endothelium -- Macrophages -- Inflammation -- Hemostasis -- Snake venom; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2019.09.009
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: M. t. tener whole venom can induce pro-inflammatory and hemostatic effects in mice. Pro-coagulant and pro-inflammatory properties in LSEC were seen after activation with venom. Pro-inflammatory cytokines release in macrophages were detected at 24 h. Both cell activation and the whole venom contribute to the immune response and the hemostactic disorder seen in vivo. Abstract: An acute inflammatory response, cellular infiltrates, anemia, hemorrhage and endogenous fibrinolysis activation were previously described in C57BL/6 mice injected with M. tener tener venom ( Mtt ). As the endothelium and innate immunity may participate in these disturbances and due to our poor understanding of the alterations produced by these venoms when the neurotoxic component is not predominant, we evaluated the effects in an in vitro model. At 24 h, the release of pro-inflammatory mediators was detected in peritoneal macrophages. At different times, the release of pro-inflammatory (TNF-α, IL-6, NO and E-Selectin), pro-coagulant (vWF and TF) and pro-fibrinolytic (uPA) mediators were seen in liver sinusoidal endothelial cells (LSECs). These results suggest that Mtt venom activates macrophages and endothelium, thus inducing the release of mediators, such as TNF-α, that orchestrate the acute inflammatory response and the later infiltration of mononuclear cells into liver in C57BL/6 mice. In addition, endothelium activation promotes TF expression, which may in turn modulate the inflammatory and hemostatic response. These findings suggest crosstalk between inflammation and hemostasis in the alterations observed in Micrurus envenomation, where the neurotoxic manifestations do not predominate.