Microglial cells are resident macrophages of the central nervous system (CNS) that respond to bioactive lipids such as docosahexaenoic acid (DHA). Low micromolar concentrations of DHA typically promote anti-inflammatory functions of microglia, but higher concentrations result in a form of pro-inflammatory programmed cell death known as pyroptosis. This study used scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to investigate the morphological characteristics of pyroptosis in BV-2 microglial cells following exposure to 200 µM DHA. Vehicle-treated cells are characterized by extended processes, spine-like projections or 0.4 to 5.2 µm in length, and numerous extracellular vesicles (EVs) tethered to the surface of the plasma membrane. In contrast to vehicle-treated cells, gross abnormalities are observed after treating cells with 200 µM DHA for 4 h. These include the appearance of numerous pits or pores of varying sizes across the cell surface, structural collapse and flattening of the cell shape. Moreover, EVs and spines were lost following DHA treatment, possibly due to release from the cell surface. The membrane pores appear after DHA treatment initially measured ~ 30 nm, consistent with the previously reported gasdermin D (GSDMD) pore complexes. Complete collapse of cytoplasmic organization and loss of nuclear envelope integrity were also observed in DHA-treated cells. These processes are morphologically distinct from the changes that occur during cisplatin-induced apoptosis, such as the appearance of apoptotic bodies and tightly packed organelles, and the maintenance of EVs and nuclear envelope integrity. Cumulatively, this study provides a systematic description of the ultrastructural characteristics of DHA-induced pyroptosis, including distinguishing features that differentiate this process from apoptosis.

中文翻译：

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DHA诱导的细胞凋亡的超微结构特征。

小胶质细胞是中枢神经系统（CNS）的常驻巨噬细胞，对诸如二十二碳六烯酸（DHA）等生物活性脂质有反应。低摩尔浓度的DHA通常会促进小胶质细胞的抗炎功能，但较高浓度的DHA会导致某种形式的促炎性程序性细胞死亡，称为烧伤。这项研究使用扫描电子显微镜（SEM）和透射电子显微镜（TEM）来研究BV-2小胶质细胞暴露于200 µM DHA后的细胞凋亡的形态特征。媒介物处理过的细胞的特征是过程延长，脊柱状突起或长度为0.4至5.2 µm，并且许多细胞外囊泡（EVs）拴在质膜表面。与载剂处理过的细胞相比，用200 µM DHA处理细胞4小时后，观察到总体异常。这些包括在整个细胞表面上出现许多大小不一的凹坑或孔，结构塌陷和细胞形状变平。此外，DHA处理后，EV和棘突丢失，可能是由于从细胞表面释放所致。DHA处理后最初测得的膜孔为〜30 nm，这与先前报道的gasdermin D（GSDMD）孔复合物一致。在DHA处理的细胞中也观察到细胞质组织完全崩溃和核被膜完整性丧失。这些过程在形态上不同于顺铂诱导的细胞凋亡过程中发生的变化，例如凋亡小体和紧密堆积的细胞器的出现，以及电动汽车和核包膜完整性的维持。