Inflammatory events induced by Loxosceles spiders' venom and sphingomyelinases D

• Grant number: 11/51957-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2012
• End date: March 31, 2013
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Denise Vilarinho Tambourgi
• Grantee: Daniel Manzoni de Almeida
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Envenomation by spiders of the genus Loxosceles, found in temperate and tropical regions of Americas, Africa and Europe, can lead to local dermonecrosis and serious systemic effects. The main toxic component in the venom of these spiders is sphingomyelinase D (SMase D), an enzyme capable of hydrolyzing lysophospatidylcholine and sphingomieline and various isoforms this toxin are present in Loxosceles venoms. The Immunochemistry Laboratory studies showed that the venom of L. intermedia and SMase D are able to induce, in mice, a systemic inflammatory process similar to endotoxic shock, howeverthe molecular mechanism involved in toxic effects have been poorly studied. The aim of this study is to establish a model using human whole blood for the study of endotoxic-like shock triggered by the venom of L. intermedia and SMase D. Thus, will be used for human blood samples that will be stimulated with venom of L. intermedia and SMase D, and then evaluated parameters related to endotoxic shock including the production of cytokines TNF-α, IL-1, IL-6 and IL-8, production of nitric oxide and reactive oxygen species, expression of markers cellular activation. Still, it is verified the participation of the complement system in the activation of leukocytes during endotoxic shock-like toxins triggered by the venom. The results allow for a better understanding of the mechanisms involved in the establishment of systemic inflammatory condition, similar to endotoxic shock, after envenenamation by Loxosceles spider, and enables the analysis of therapeutic alternatives for the effects toxics during the loxoscelism (AU)