Role of lipid mediators derived from the metabolism of 5-lipoxygenase in granuloma formation induced by S. mansoni eggs

• Grant number: 11/08622-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2011
• End date: September 30, 2013
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Fabiani Gai Frantz
• Grantee: Gabriel Toffoli da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

According to WHO, it is estimated that worldwide there are approximately 2 billion people infected with intestinal helminths, and the number of people who are cured of these diseases is low, resulting in a large percentage of chronically infected individuals. It is one of the most important parasitic diseases present in developing countries, becoming a serious public health problem, directly related to poverty and social disadvantage. Established infection parasite eggs fall into the bloodstream and are trapped in the microvasculature (capillary network) of the liver, where there is a strong granulomatous response and the formation of fibrosis. These factors together are responsible for the morbidity in infected individuals, and in some cases, can be lethal. The cellular composition of granulomas induced by eggs of S. mansoni including eosinophils, macrophages, lymphocytes, neutrophils, mast cells and fibroblasts. In an experimental model, granulomas develop in the lungs of mice after intravenous injection of eggs. It is observed progressive induction of TH1-type immune responses (IFN-g, with low levels of IL-4 and IL-13), involving mainly by mononuclear cells and little collagen deposition. This transient response is a TH2 profile, with lesions containing mononuclear cells, eosinophils and fibroblasts, with significant collagen deposition characteristic of type 2 granulomas. Leukotrienes (LTs) are lipid mediators derived from arachidonic acid metabolites via the 5-lipoxygenase (5LO). LTs are potent proinflammatory agents and induce recruitment, cellular activation, regulation of microbicidal activity of polymorphonuclear and monunucleares, and therefore, protect against different infectious agents. However, to date no one knows the mechanism by which lipid mediators derived from the 5-LO pathway is involved in granuloma induced by eggs of S. mansoni. In this study, mice deficient enzyme 5LO-KO will be inoculated with the helminth eggs for evaluation of immunopathological parameters involved in the induction of type 2 granulomas. (AU)