STIM1 but not STIM2 is an essential regulator of Ca2+ influx-mediated NADPH oxidase activity in neutrophil-like HL-60 cells.

摘要: Extracellular Ca2+ entry, primarily mediated through store-operated entry (SOCE), is known to be a critical event for NADPH oxidase (NOX2) regulation in neutrophils. While defective NOX2 activity has been linked various inflammatory diseases, regulatory mechanisms that control influx-induced activation are poorly understood SOCE. The role of STIM1, sensor transduces the store depletion signal plasma membrane, seems well established and supported by numerous studies non-phagocytic cells. Here, neutrophil-like HL-60 cells we used siRNA approach delineate effect STIM1 knock-down on regulated influx. Because function homolog, STIM2, still unclear, determined consequence STIM2 NOX2. was effective isoform specific when assayed real-time PCR Western blotting. Consistent with unique SOCE, but not significantly decreased influx induced fMLF or SERCA pump inhibitor thapsigargin. A redistribution originally localized intracellularly, near membrane observed confocal microscopy upon stimulation fMLF. Inhibition STIM1-induced SOCE led marked decrease while had no effect. Thus, our results provide evidence protein neutrophils excluding involvement this process. It also places as key modulator potential interest anti-inflammatory pharmacological development.