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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >The inhibitory effect of secretory leukocyte protease inhibitor (SLPI) on formation of neutrophil extracellular traps
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The inhibitory effect of secretory leukocyte protease inhibitor (SLPI) on formation of neutrophil extracellular traps

机译：分泌型白细胞蛋白酶抑制剂（SLPI）对中性粒细胞胞外陷阱形成的抑制作用

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摘要

Neutrophil extracellular traps (NETs), web-like DNA structures, provide efficient means of eliminating invading microorganisms but can also present a potential threat to its host because it is a likely source of autoantigens or by promoting bystander tissue damage. Therefore, it is important to identify mechanisms that inhibit NET formation. Neutrophil elastase (NE)dependent chromatin decondensation is a key event in the release of NETs release. We hypothesized that inhibitors of NE, secretory leukocyte protease inhibitor (SLPI) and alpha(1)-proteinase inhibitor (alpha(1)-PI), has a role in restricting NET generation. Here, we demonstrate that exogenous human SLPI, but not alpha(1)-PI markedly inhibited NET formation in human neutrophils. The ability of exogenous SLPI to attenuate NET formation correlated with an inhibition of a core histone, histone 4 (H4), cleavage, and partial dependence on SLPI-inhibitory activity against NE. Moreover, neutrophils from SLPI (/) mice were more efficient at generating NETs than were neutrophils from wild-type mice in vitro, and in experimental psoriasis in vivo. Finally, endogenous SLPI colocalized with NE in the nucleus of human neutrophils in vitro, as well as in vivo in inflamed skin of patients with psoriasis. Together, these findings support a controlling role for SLPI in NET generation, which is of potential relevance to infectious and autoinflammatory diseases.
机译：中性粒细胞胞外诱捕器（NETs）呈网状DNA结构，提供了消除入侵微生物的有效方法，但由于它可能是自身抗原的来源或通过促进旁观者组织破坏，因此也可能对其宿主构成潜在威胁。因此，确定抑制NET形成的机制很重要。中性粒细胞弹性蛋白酶（NE）依赖的染色质去缩合是NETs发行中的关键事件。我们假设NE的抑制剂，分泌性白细胞蛋白酶抑制剂（SLPI）和alpha（1）-蛋白酶抑制剂（alpha（1）-PI），在限制NET产生中起作用。在这里，我们证明，外源的人类SLPI，但不是alpha（1）-PI明显抑制人类嗜中性白细胞的NET形成。外源性SLPI减弱NET形成的能力与抑制核心组蛋白，组蛋白4（H4），裂解以及部分依赖SLPI抑制NE的活性有关。此外，在体外和在实验性牛皮癣中，来自SLPI（/）小鼠的中性粒细胞比来自野生型小鼠的中性粒细胞更能产生NET。最后，在牛皮癣患者发炎的皮肤中以及体内，内源性SLPI与NE在人嗜中性粒细胞核中共定位。总之，这些发现支持了SLPI在NET生成中的控制作用，这与传染性和自发性疾病具有潜在的相关性。

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