Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Sep 4:10:2082.
doi: 10.3389/fimmu.2019.02082. eCollection 2019.

Inflammation Induced by Platelet-Activating Viperid Snake Venoms: Perspectives on Thromboinflammation

Catarina Teixeira  1   2 , Cristina Maria Fernandes  1   2 , Elbio Leiguez  1   2 , Ana Marisa Chudzinski-Tavassi  2   3
Affiliations
Review

Inflammation Induced by Platelet-Activating Viperid Snake Venoms: Perspectives on Thromboinflammation

Catarina Teixeira et al. Front Immunol. .

Abstract

Envenomation by viperid snakes is characterized by systemic thrombotic syndrome and prominent local inflammation. To date, the mechanisms underlying inflammation and blood coagulation induced by Viperidae venoms have been viewed as distinct processes. However, studies on the mechanisms involved in these processes have revealed several factors and signaling molecules that simultaneously act in both the innate immune and hemostatic systems, suggesting an overlap between both systems during viper envenomation. Moreover, distinct classes of venom toxins involved in these effects have also been identified. However, the interplay between inflammation and hemostatic alterations, referred as to thromboinflammation, has never been addressed in the investigation of viper envenomation. Considering that platelets are important targets of viper snake venoms and are critical for the process of thromboinflammation, in this review, we summarize the inflammatory effects and mechanisms induced by viper snake venoms, particularly from the Bothrops genus, which strongly activate platelet functions and highlight selected venom components (metalloproteases and C-type lectins) that both stimulate platelet functions and exhibit pro-inflammatory activities, thus providing insights into the possible role(s) of thromboinflammation in viper envenomation.

Keywords: platelet activation; snake envenoming; thromboinflammation; toxins; venom-induced inflammation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic representation of the interplay between inflammation and alteration of the hemostatic system induced by venom and toxins that can favor thromboinflammation. The viperid snake venoms- and toxins-induced tissue injury trigger defense mechanisms in the victims, characterized by inflammation and hemostatic responses. Release of a multitude of mediators and signaling molecules that simultaneously act in the innate immune and hemostasis systems occurs, suggesting an overlap between both systems during viper envenomation. This interplay between inflammation and hemostatic alterations can characterize thromboinflammation. (A) Inflammation induced by snake venoms and toxins is characterized by migration of leukocytes, activation of cells (leukocytes and endothelial cells), which produce and release local and systemic pro-inflammatory mediators (IL-1β, IL-6, IL-8, TNF-α, MIP-1α, NO, histamine, serotonin, PAF, bradykinin, PGE2, TXA2, LTB4, and RANTES), generation of anaphylatoxins (C3 and C5) in blood plasma and DAMPs from extracellular matrix and cellular lysis. (B) Venoms and toxins induce hemostatic alterations, including platelet activation and aggregation, thrombin generation and suppression of the fibrinolytic system. Pro-coagulant toxins (prothrombin activators, thrombin-like enzymes, factor X and V activators), activate the expression of pro-thrombotic and pro-fibrinolytic molecules (vWfactor, tissue factor, fibrinogen, C5, and C3), which Interact with surface receptors (PAR-1, PAR-4, GPIb-IX-V, GPVI, TLR2, and TLR4) on platelets. Moreover, the activation of platelets by SV-CLRPs occurs in a non-enzymatic manner by interaction of toxins with the receptor CLEC-2. Several factors and signaling molecules of hemostatic system interfere with innate immune system, resulting in the amplification of inflammatory process and vice-versa.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood. (2019) 133:906–18. 10.1182/blood-2018-11-882993 - DOI - PubMed
    1. Gragnano F, Sperlongano S, Golia E, Natale F, Bianchi R, Crisci M, et al. . The role of von Willebrand factor in vascular inflammation: from pathogenesis to targeted therapy. Mediators Inflamm. (2017) 2017:5620314. 10.1155/2017/5620314 - DOI - PMC - PubMed
    1. Chauhan AK, Kisuka J, Brill A, Walsh MT, Scheiflinger F, Wagner DD. ADAMTS13: a new link between thrombosis and inflammation. J Exp Med. (2008) 205:2065–74. 10.1084/jem.20080130 - DOI - PMC - PubMed
    1. Massberg S, Grahl L, von Bruehl ML, Manukyan D, Pfeiler S, Goosmann C, et al. . Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. (2010) 16:887–96. 10.1038/nm.2184 - DOI - PubMed
    1. Ekdahl KN, Teramura Y, Hamad OA, Asif S, Duehrkop C, Fromell K, et al. . Dangerous liaisons: complemente, coagulation, and kallikrein/kinin cross-talk act as linchpin in the events leading to thromboinflammation. Immunol Rev. (2016) 274:245–69. 10.1111/imr.12471 - DOI - PubMed

Publication types