Role of the Platelet-activating factor (PAF) on neuronal nitric oxide synthase (nNOS) in human dendritic cells

• Grant number: 19/26602-3
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2020
• Effective date (End): August 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal researcher: Jose Alexandre Marzagão Barbuto
• Grantee: Victor Massatoshi Kawakami Tsuda
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Dendritic cells are the main professional antigen-presenting cells of the human body, having a major role in the innate and adaptive immune responses. It has been researched a lot about the effects of different cytokines on these cells, however, recent studies - highlighting the molecular biology field - suggest that knowledge about the metabolism of the dendritic cells may be essential for treating the second major cause of death worldwide: cancer. To do all of its antigen-presenting and lymphocyte-activating functions correctly, the dendritic cells must go through transient steps of metabolic switches concerning glycolysis and oxidative phosphorylation in order to fulfill its process of maturation. These changes are due to nitric oxide (NO) signaling, being one of the key enzymes in the human dendritic cell maturation mechanism the neuronal nitric oxide-synthase (nNOS). Many factors and biochemical pathways regulate the activity of this enzyme, with emphasis on the Platelet Activating Factor-like (PAF-like) phospholipids which are generated in the tumoral microenvironment. Therefore, the observation and comprehension of the effect of those molecules on human nNOS may contribute to a more effective interference in the tumor mechanisms that are responsible for inhibiting the imune response in the tumoral microenvironment.