Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, INRS-Institut Armand-Frappier, Université du Québec, Laval, QC, Canada.
Mediators Inflamm. 2012;2012:198382. doi: 10.1155/2012/198382. Epub 2012 May 8.
Despite the fact that Esenbeckia leiocarpa, a Brazilian plant, possesses potential anti-inflammatory properties, its effect in neutrophils, key players in inflammation, has never been investigated. In this study, a crude hydroalcoholic extract (CHE) was used to evaluate the potential toxic or agonistic effect of E. leiocarpa in human neutrophils. At a noncytotoxic concentration of 500 μg/mL, CHE increased actin polymerization and cell signaling events, especially p38 MAPK. Its modulatory activity on neutrophil cell apoptosis was investigated by cytology and by flow cytometry and, although CHE increased the apoptotic rate (by cytology) and increased annexin-V binding, it did not, unexpectedly, increase CD16 shedding. CHE increased the degradation of the cytoskeletal proteins gelsolin and paxillin but, surprisingly, not of vimentin. The proapoptotic activity of CHE was reversed by a pan-caspase inhibitor but not by a p38 inhibitor. We conclude that CHE is a novel human neutrophil agonist that induces apoptosis by a caspase-dependent and p38-independent mechanism in an atypical fashion based on its lack of effect on CD16 shedding and vimentin degradation. Since the resolution of inflammation occurs by elimination of apoptotic neutrophils, the ability of CHE to induce neutrophil apoptosis correlates well with its anti-inflammatory properties, as previously reported.
尽管巴西植物 Esenbeckia leiocarpa 具有潜在的抗炎特性，但它对炎症关键细胞——中性粒细胞的影响从未被研究过。在这项研究中，使用粗水醇提取物（CHE）来评估 E. leiocarpa 对人中性粒细胞的潜在毒性或激动作用。在非细胞毒性浓度 500μg/ml 时，CHE 增加了肌动蛋白聚合和细胞信号事件，特别是 p38 MAPK。通过细胞学和流式细胞术研究了其对中性粒细胞细胞凋亡的调节活性，尽管 CHE 增加了细胞凋亡率（通过细胞学）并增加了膜联蛋白-V 结合，但出乎意料的是，它并没有增加 CD16 脱落。CHE 增加了细胞骨架蛋白凝胶蛋白和桩蛋白的降解，但令人惊讶的是，它没有降解波形蛋白。CHE 的促凋亡活性被泛半胱天冬酶抑制剂逆转，但不被 p38 抑制剂逆转。我们得出结论，CHE 是一种新型的人中性粒细胞激动剂，通过一种 caspase 依赖性和 p38 非依赖性机制诱导细胞凋亡，这种机制不寻常，表现在它对 CD16 脱落和波形蛋白降解没有影响。由于炎症的消退是通过消除凋亡的中性粒细胞来实现的，因此 CHE 诱导中性粒细胞凋亡的能力与之前报道的其抗炎特性很好地相关。
