LAUSR

Macrophages are a heterogeneity population implicated in several diseases and correlated with distinct tissue outcomes after injury. M2 macrophages have been associated with tissue repair whereas M1 macrophages participate in early phase of tissue damage. Recent works have also suggested that upon activation, macrophages can use distinguished nutrients as source of energy and these metabolic pathways lead to their activation and differentiation. Nutrient sensors are intimae associated with innate receptors and therefore connected with inflammatory response. Uric acid is a damage-associated molecular pattern (DAMP), released from ischemic tissues and dying cells which, when crystalized, is able to activate the NLRP3 inflammasome through frustrated phagocytosis. Soluble uric acid (sUA) is found in high concentrations in the serum of great apes, and even higher levels in some diseases, before the appearance of crystals. sUA can be released in a hypoxic environment and triggers NLRP3 through the production of mitochondrial ROS, with increased maximum and reserve oxygen consumption ratio (OCR) and higher VDAC protein levels. This process is followed by ASC speck formation, caspase-1 activation and IL-1β release. These findings may have profound implications for inflammatory-related diseases. Support: FAPESP and CNPq. Disclosure of Interest N. Camara Grant/research support from: FAPESP, CNPq