Uridine-Diphosphate-Glucose (UDP-G) Activates Oxidative Stress and Respiratory Burst in Isolated Neutrophils

LAIRION F; CARBIA, C; CHIESA, I; SAPORITO MAGRIÑÁ, CHRISTIAN; BORDA NATALIA; LAZAROWSKI ALBERTO; REPETTO, MARISA GABRIELA

Pharmaceuticals

MDPI

Año: 2023 vol. 16

Extracellular purinergic agonist uridine diphosphate glucose (UDP-G) activates chemotaxis of human neutrophils (PMN) and the recruitment of PMN at the lung level, via P2Y14 purinergic receptor signaling. This effect is similar to the activation of PMN with N-formyl-methionyl- leucyl-phenylalanine (fMLP), a mechanism that also triggers the production of superoxide anion and hydrogen peroxide via the NADPH oxidase system. However the effects of UDP-G on this system have not been studied. Defects in the intracellular phagocyte respiratory burst (RB) cause in affected patients recurrent infections, immunodeficiency, chronic and severe diseases, often with sepsis and hypoxia. The extracellular activation of PMN by UDP-G could affect the RB and oxidative stress (OS) in situations of inflammation, infection and/or sepsis. Association of PMNs activation by UDP-G with OS and RB was studied. OS was evaluated by measuring spontaneous chemiluminescence (CL) of PMNs with a scintillation photon counter, and RB by measuring oxygen consumption with an oxygen Clark electrode at 37 °C, in non stimulated cells and after activation (15 min) with lipopolysacharides (LPS, 2 µg/mL), phorbol myristate acetate (PMA, 20 ng/mL) or UDP-G (100 mM). The stimulation index (SI) was calculated in order to establish the activation effect of the three agonists. After stimulation with LPS or PMA, the activated PMNs (0.1 x 106 cells/mL) showed an increase in CL (35%, p