pβ-NADsup+/supsube/sub (extracellular β-NADsup+/sup), present at nanomolar levels in human plasma, has been implicated in the regulation of [Casup2+/sup]subi/sub (the intracellular calcium concentration) in various cell types, including blood cells, by means of different mechanisms. Here, we demonstrate that micromolar NADsup+/supsube/sub (both the α and the β extracellular NADsup+/sup forms) induces a sustained [Casup2+/sup]subi/sub increase in human granulocytes by triggering the following cascade of causally related events: (i) activation of adenylate cyclase and overproduction of cAMP; (ii) activation of protein kinase A; (iii) stimulation of ADP-ribosyl cyclase activity and consequent overproduction of cADP-ribose, a universal Casup2+/sup mobilizer; and (iv) influx of extracellular Casup2+/sup. The NADsup+/supsube/sub-triggered [Casup2+/sup]subi/sub elevation translates into granulocyte activation, i.e. superoxide and nitric oxide generation, and enhanced chemotaxis in response to 0.1–10 μM NADsup+/supsube/sub. Thus extracellular β-NADsup+/supsube/sub behaves as a novel pro-inflammatory cytokine, stimulating human granulocytes and potentially recruiting them at sites of inflammation./p
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机译：在人血浆中以纳摩尔浓度存在的>β-NAD + e （细胞外β-NAD + ）与该疾病有关。通过不同的机制调节包括血细胞在内的各种细胞类型中[Ca 2 + ] i （细胞内钙的浓度）。在这里，我们证明了微摩尔NAD + e （α和β细胞外NAD + 形式）诱导持续的[Ca 通过触发以下因果相关事件的级联反应，人类粒细胞增加2 + ] i ：（i）腺苷酸环化酶激活和cAMP过度生产; （ii）激活蛋白激酶A; （iii）刺激ADP-核糖基环化酶的活性，从而导致cADP-核糖（一种普遍的Ca 2 + 动员）过量生产; （iv）细胞外Ca 2 + 的流入。 NAD + e 触发的[Ca 2 + ] i 升高转化为粒细胞活化，即超氧化物和硝酸NAD + e 产生的氧化氮和增强的趋化性。因此，细胞外β-NAD + e 表现为新型促炎细胞因子，刺激人粒细胞并可能在炎症部位募集它们。
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