Complement system inhibition as means for controlling inflammation associated to envenomations

• Grant number: 19/27348-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2020
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Denise Vilarinho Tambourgi
• Grantee: Dayanne Carla Fernandes
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

The complement system, one of the first lines of defense of the innate immunity, is a major mechanism by which the body recognizes foreign substances and pathogens. This system consists of over 40 proteins, among them regulators and membrane-bound receptors and plasma proteins that interact with multiple cells and mediators of the immune system. These interactions vary according to the pathophysiologic context and occur at different stages of the immune reaction. The dysregulation of the complement activation often results in acute or chronic inflammation and can contribute to the development of several diseases. Venoms from poisonous animals contain a plethora of toxic molecules including many proteolytic enzymes. These proteolytic enzymes have a range of functions in the pathology caused by the envenomation and some may aid to immobilize and/or kill the prey. In nature a wide range of animal venoms and animal secretions are found to interact with complement system, which activation can contribute to both the spread of the venom and the inflammatory response. So far, therapeutic strategies for treating accidents by poisonous animals not always reliable include antivenom, corticosteroids, vasopressors, infusion of platelets, catecholamines, hyperbaric oxygenation, etc. An in-depth characterization of the action of venoms on the activation of the complement system as well as the use of complement inhibitors in experimental models of envenomation may shed light on potentially specific therapies targeting this pathway. Thus, the aim of this project is to investigate the possible therapeutic use of complement inhibitors to prevent or reduce venoms local/systemic pathologies. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERNANDES, DAYANNE CARLA; TAMBOURGI, DENISE V.. Complement System Inhibitory Drugs in a Zebrafish (Danio rerio) Model: Computational Modeling. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 18, p. 20-pg., 2023-09-01. (13/07467-1, 19/27348-3)

BOTOSSO, VIVIANE FONGARO; CALIL JORGE, SORAIA ATTIE; ASTRAY, RENATO MANCINI; DE SA GUIMARAES, ANA MARCIA; MATHOR, MONICA BEATRIZ; DE CARNEIRO, PATRICIA DOS SANTOS; DURIGON, EDISON LUIZ; COVAS, DIMAS; LEAL DE OLIVEIRA, DANIELLE BRUNA; OLIVEIRA, RICARDO DAS NEVES; et al. Anti-SARS-CoV-2 equine F (Ab ')(2) immunoglobulin as a possible therapy for COVID-19. SCIENTIFIC REPORTS, v. 12, n. 1, p. 17-pg., 2022-03-10. (13/26450-2, 14/11513-1, 20/07251-2, 20/09149-0, 13/07467-1, 18/04609-3, 19/27348-3, 20/05293-0, 19/12303-4)

FERNANDES, DAYANNE CARLA; SILVA-DE-FRANCA, FELIPE; POHL, PAULA CRISTIANE; ETO, SILAS FERNANDES; SARDINHA, LUIZ ROBERTO; LAMBRIS, JOHN D.; TAMBOURGI, DENISE, V. Cp40-mediated complement C3 inhibition dampens inflammasome activation and inflammatory mediators storm induced by Bitis arietans venom. International Immunopharmacology, v. 147, p. 17-pg., 2025-01-13. (13/07467-1, 19/27348-3)