Contributions of the Complement System and Endothelial Cells in the Immunopathology of Envenomations by Africanized Honey Bees (Apis mellifera)

• Grant number: 24/17031-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Denise Vilarinho Tambourgi
• Grantee: Felipe Silva de França
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

Uncontrolled inflammatory events have been associated with a variety of clinical conditions, as they can lead to tissue damage, organ dysfunction, and even death, particularly in cases of envenomations by venomous animals. In recent years, envenomations caused by stings from Africanized honey bees (Apis mellifera) have significantly increased in Brazil. These incidents can present distinct clinical and laboratory characteristics, influenced by factors such as prior sensitization of patients and the amount of venom injected.Given these factors, four clinical scenarios can be observed in envenomated individuals: 1) local inflammatory reactions, 2) allergic manifestations, 3) anaphylactic shock, and/or 4) systemic toxic reactions. Although these scenarios involve different molecular and cellular elements, a common feature is the presence of circulatory alterations, which result in extensive oedema formation, systemic vasodilation, shock, and hypo- and hypertension. These changes can contribute to renal failure and even death observed in cases of envenomation. Despite their significance, the molecular, cellular, and inflammatory events governing these alterations are not yet fully understood.Studies have shown that patients attacked by swarms exhibit elevated levels of venom in circulation for several days and weeks following envenomation. The venom from Africanized bees (AmV) is known to be highly cytotoxic to circulating erythrocytes. However, the effects of AmV toxins on other components of the bloodstream, such as the complement system and endothelial cells, and the interaction between these elements during envenomations remain to be investigated. Notably, literature reports cases of patients attacked by swarms who exhibited complementopathy, characterized by a drastic reduction in circulating levels of the central complement component, protein C3.Preliminary data from our group suggest that AmV acts as a potential activator of the human complement system, as it induces the generation of anaphylatoxins C3a, C4a, and C5a, as well as the soluble C5b-9 complex in normal human serum models. Additionally, in models of human whole blood, AmV causes an increase in circulating levels of DAMPs related to erythrocyte destruction, as well as elevated concentrations of various chemokines and eicosanoids. These effects of AmV in different experimental models indicate that inflammatory events may lead to circulatory alterations that contribute to the immunopathology of the various clinical manifestations of envenomations by Africanized honey bees.Thus, the present study aims to investigate the direct effects of AmV, both in isolation and in interaction with the complement system and other inflammatory mediators, as well as the DAMPs released by the action of AmV toxins on endothelial cells in vitro. Analysing the contribution of these elements to the pathophysiological aspects of envenomation in vivo is essential for a better understanding and management of cases of envenomation by Africanized honey bees.