Study of the action of fatty acids on leukocytes

Abstract

Previous studies of our group (93/3498-4, 98/11714-2) have determined that fatty acids (FA) can function as signaling factors in intercellular interactions, regulating several aspects of leukocyte function (mainly lymphocytes and macrophages) and insulin secretion by beta cells of pancreatic islets. In this project we focus the investigation on the mechanisms of action of fatty acids. The first site of interaction of fatty acids in the cell is the plasma membrane what leads us to investigate the interactions between FA and the lipid bilayer in model membranes and isolated cells. The effects of FA in the intracellular signaling pathways will be investigated as well as the involvement of receptors (like the PPAR) and transcription factors (NFκB and AP1). In Langerhans islets the effects of FA in the signaling pathways to insulin and in the activation of the enzymatic complex NADPH oxidase (that was identified by us in rat Langerhans islets) will be investigated. The toxicity of FA has been clearly evidenced by our group in lymphocytes and macrophages and will be now studied in neutrophils, using in vivo and in vitro models. The persistence (or exacerbation) of the effects of FA administration, particularly fish oil, will be assessed by its administration during two generations of rats. These issues complete our investigation on the mechanisms of action of FA. It is necessary to determine if the toxicity of FA occurs indistinctly for all leukocytes and if the use of fish oil (as alimentary supplement) can modify the immune function and ensure a better life quality to our descendents. (AU)