Complement Activation by Animal Venoms

Abstract

During activation of complement (C) system, C4b and C3b attach covalently to targets such as cell membranes. Deposited C4b serve both as the focus for the assembly of the C3 convertases and as ligands for C3b receptors or inactivators. C4a, C3a and C5a, mediators of the early events of inflammation, are released into the fluid phase while C5b serves to organize the cytolytical complex C5b-C9. Among the Arthropoda the venom from some spiders (Loxosceles) contain activators of the mammalian C system, although the exact mechanism and point of the activation cascade in where they act were not yet elucidated. In the insect venoms as honeybee, yellow jacket, yellow hornet, white-facet hornet, caterpillars and wasp there are some components capable of reducing total haemolytic and serum levels. Interestingly, mellitin, a soluble haemolytic peptide present in bee venom shares structural homology with human C9. Scorpion venom apparently are not active on the C system. Snakes, belonging to ELAPIDAE, CROTALIDAE and VIPERIDAE families produce venoms containing components with a vast range of action on mammalian C system, some acting by cleaving directly a particular component, while others interact with C components, the resulting complex being able as an amplificator, to activate part of the C cascade. Soluble mediators of inflammation, cell bound fragments of C components recognizable by specific receptors disposed on immune or inflammatory cells, or the formation of multimolecular complex potentially capable of damage host cells are the presumable consequences of C activation by animal venoms.