Venom fromBothrops lanceolatus, a Snake Species Native to Martinique, Potently Activates the Complement System

Abstract

Bothrops lanceolatus snake venom causes systemic thrombotic syndrome but also local inflammation involving extensive oedema, pain, and haemorrhage. Systemic thrombotic syndrome may lead to fatal pulmonary embolism and myocardial and cerebral infarction. Here, we investigated the ability of B. lanceolatus venom to activate the Complement system (C) in order to improve the understanding of venom-induced local inflammation. Data presented show that B. lanceolatus venom is able to activate all C-pathways. In human serum, the venom strongly induced the generation of anaphylatoxins, such as C5a and C4a, and the Terminal Complement complex. The venom also induced cleavage of purified human components C3, C4, and C5, with the production of biologically active C5a. Furthermore, the venom enzymatically inactivated the soluble C-regulator and the C1-inhibitor (C1-INH), and significantly increased the expression of bound C-regulators, such as MCP and CD59, on the endothelial cell membrane. Our observations that B. lanceolatus venom activates the three Complement activation pathways, resulting in anaphylatoxins generation, may suggest that this could play an important role in local inflammatory reaction and systemic thrombosis caused by the venom. Inactivation of C1-INH, which is also an important inhibitor of several coagulation proteins, may also contribute to inflammation and thrombosis. Thus, further in vivo studies may support the idea that therapeutic management of systemic B. lanceolatus envenomation could include the use of Complement inhibitors as adjunct therapy.

C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera

“…Current understanding indicates that snake venoms trigger complement activation in humans (27)(28)(29)(30)(31)(32)(33)(34)(35)(36), but the overall molecular mechanisms induced by the envenomation have remained underexplored. Here, by coupling in vitro and in vivo approaches, we have determined that N. annulifera venom induces reduction in complement pathways activity, anaphylatoxins generation and sTCC assembly.…”

“…In addition, venoms from snakes of different genera, such as Trimeresurus, Bothrops, and Micrurus, have been shown to trigger complement activation in normal human serum (NHS) in vitro, leading to anaphylatoxin generation and soluble Terminal Complement Complex (sTCC) assembly. These events are in part associated with the action of snake venom metalloproteinases (SVMP) and snake venom serine proteinases (SVSP) on central complement components and regulators (27)(28)(29)(30)(31)(32)(33). In addition, other studies have demonstrated depletion of C3 and Factor B (34) and an increase in anaphylatoxins and sTCC plasma levels in envenomated patients, indicating complement activation (35,36).…”

Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

“…B. lanceolatus venom can activate all three complement-pathways. In an ex vivo human blood assay, this venom strongly induced the generation of anaphylatoxins, such as C3a, C4a, C5a and the soluble terminal complement complex [211,212]. Venoms from numerous other species from the genus Bothrops are able to activate the complement system by one or several activation pathways, generating high quantities of anaphylatoxins by directly cleaving C3 and C5 or by inactivating the regulator C1-INH.…”

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

“…In this regard, activation of the complement cascade by 19 different Bothrops species from South and Central America was demonstrated to occur by one or more pathways through their action either by directly cleaving C3 and C5 factors or by inactivating the soluble C1 inhibitor, C1-INH factor (71, 72). Moreover, activation of the complement system by B. lanceolatus snake venom in human serum has been reported (101).…”