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从毒液中分离出的天冬氨酸49磷脂酶A作用下的人中性粒细胞功能

Human neutrophils functionality under effect of an Asp49 phospholipase A isolated from venom.

作者信息

Setúbal Sulamita da S, Pontes Adriana S, Nery Neriane M, Rego Cristina M A, Santana Hallison M, de Lima Anderson M, Boeno Charles N, Paloschi Mauro V, Soares Andreimar M, Zuliani Juliana P

机构信息

Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz (FIOCRUZ) Rondônia, Porto Velho, RO, Brazil.

Centro de Estudos de Biomoléculas Aplicadas à Saúde (CEBio), Fundação Oswaldo Cruz, (FIOCRUZ) Rondônia e Departamento de Medicina, Universidade Federal de Rondônia (UNIR), Porto Velho, RO, Brazil.

出版信息

Toxicon X. 2020 Mar 18;6:100032. doi: 10.1016/j.toxcx.2020.100032. eCollection 2020 Jun.

Abstract

envenomation is associated with a cellular inflammatory response, characterized by pronounced neutrophil infiltration at the site of injury. Neutrophils act as the first line of defence, owing to their ability to migrate to the infected tissue, promoting an acute inflammatory response. At the site of inflammation, neutrophils perform defence functions such as phagocytosis, release of proteolytic enzymes, generation of reactive oxygen species (ROS), and synthesis of inflammatory mediators such as cytokines and lipid mediators. Neutrophils can also form neutrophil extracellular nets (NETs), webs composed of chromatin and granule proteins. This occurs after neutrophil activation and delivers high concentrations of anti-microbial molecules to the site of injury. This study evaluated the impact of BaTX-II, an Asp49 phospholipase A (PLA) isolated from snake venom on human neutrophils At non-toxic concentrations, BaTX-II induced hydrogen peroxide production by neutrophils, and this was reduced by wortmannin, a PI3K inhibitor. BaTX-II stimulated IL-1β, IL-8, LTB, myeloperoxidase (MPO), and DNA content release, consistent with NET formation. This is the first study to show the triggering of relevant pro-inflammatory events by PLA Asp49 isolated from secretory venom.

摘要

蛇毒中毒与细胞炎症反应相关,其特征是在损伤部位有明显的中性粒细胞浸润。中性粒细胞作为第一道防线,因其能够迁移到感染组织,促进急性炎症反应。在炎症部位,中性粒细胞执行防御功能,如吞噬作用、蛋白水解酶的释放、活性氧(ROS)的产生以及炎症介质如细胞因子和脂质介质的合成。中性粒细胞还可以形成中性粒细胞胞外陷阱(NETs),即由染色质和颗粒蛋白组成的网络。这发生在中性粒细胞激活后,并将高浓度的抗菌分子输送到损伤部位。本研究评估了从蛇毒中分离出的天冬氨酸49磷脂酶A(PLA)——BaTX-II对人中性粒细胞的影响。在无毒浓度下,BaTX-II诱导中性粒细胞产生过氧化氢,而这被PI3K抑制剂渥曼青霉素所降低。BaTX-II刺激白细胞介素-1β、白细胞介素-8、白三烯B4、髓过氧化物酶(MPO)和DNA含量释放,这与NET形成一致。这是第一项显示从分泌毒液中分离出的PLA天冬氨酸49引发相关促炎事件的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85e0/7286099/8ee2f0913b1a/gr1.jpg

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