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Differences in Staining for Neutrophil Elastase and its Controlling Inhibitor SLPI Reveal Heterogeneity among Neutrophils in Psoriasis.
Journal of Investigative Dermatology ( IF 5.7 ) Pub Date : 2020-01-13 , DOI: 10.1016/j.jid.2019.12.015
Joanna Skrzeczynska-Moncznik 1 , Katarzyna Zabieglo 1 , Oktawia Osiecka 1 , Agnieszka Morytko 1 , Piotr Brzoza 1 , Lukasz Drozdz 1 , Monika Kapinska-Mrowiecka 2 , Brice Korkmaz 3 , Maciej Pastuszczak 4 , Joanna Kosalka-Wegiel 5 , Jacek Musial 5 , Joanna Cichy 1
Affiliation  

Neutrophils are broadly classified into conventional neutrophils (PMNs) and low-density granulocytes (LDGs). LDGs are better than PMNs at generating neutrophil extracellular traps (NETs), which may contribute to the pathology of autoimmune diseases. We hypothesized that LDGs and PMNs differ in their levels of unrestrained NE that supports NET generation. Here, we show that individuals with psoriasis contain elevated levels of LDGs and that in contrast to PMNs, the LDGs display higher staining for NE and lower staining for its inhibitor SLPI. The heterogeneity between blood-derived LDGs and PMNs was somewhat reminiscent of the differences in the NE and SLPI staining patterns observed in psoriasis skin-infiltrating neutrophils. Distinctive staining for NE and SLPI in LDGs and PMNs did not result from differences in their protein levels nor manifested in higher total proteolytic activity of NE in LDGs; rather, it likely depended on different cytosolic sequestration of these proteins. The disparate profile of NE and SLPI in LDGs and PMNs coincided with altered migratory responses of these cells to cutaneous chemoattractants. Collectively, differential NE and SLPI staining identifies common attributes of both circulating and skin-infiltrating neutrophils, which may guide neutrophil migration to distinct skin regions and determine the localization of LDGs-mediated cutaneous pathology.



中文翻译:

中性粒细胞弹性蛋白酶染色及其控制抑制剂SLPI的染色差异揭示了牛皮癣中性粒细胞之间的异质性。

中性粒细胞大致分为常规中性粒细胞(PMN)和低密度粒细胞(LDG)。LDG在产生嗜中性粒细胞胞外陷阱(NETs)方面比PMN更好,这可能有助于自身免疫性疾病的病理。我们假设LDG和PMN在支持NET生成的不受约束的NE的级别上有所不同。在这里,我们显示银屑病患者的LDGs含量升高,与PMN相比,LDGs对NE的染色较高,对抑制剂SLPI的染色较低。血液来源的LDG和PMN之间的异质性使人联想到在牛皮癣皮肤浸润性中性粒细胞中观察到的NE和SLPI染色模式的差异。LDG和PMN中NE和SLPI的独特染色既不是由于蛋白质水平的差异,也不是因为LDG中NE的总蛋白水解活性较高。相反,这可能取决于这些蛋白质的不同胞质隔离。LDG和PMN中NE和SLPI的不同情况与这些细胞对皮肤趋化因子迁移反应的改变相吻合。总而言之,NE和SLPI差异染色可识别循环中性粒细胞和皮肤浸润性中性粒细胞的共同属性,这可指导中性粒细胞迁移至不同的皮肤区域并确定LDGs介导的皮肤病理学的定位。LDG和PMN中NE和SLPI的不同情况与这些细胞对皮肤趋化因子迁移反应的改变相吻合。总而言之,NE和SLPI差异染色可识别循环中性粒细胞和皮肤浸润性中性粒细胞的共同属性,这可指导中性粒细胞迁移至不同的皮肤区域并确定LDGs介导的皮肤病理学的定位。LDG和PMN中NE和SLPI的不同情况与这些细胞对皮肤趋化因子迁移反应的改变相吻合。总而言之,NE和SLPI差异染色可识别循环中性粒细胞和皮肤浸润性中性粒细胞的共同属性,这可指导中性粒细胞迁移至不同的皮肤区域并确定LDGs介导的皮肤病理学的定位。

更新日期:2020-01-13
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