Chronic inflammation and infection in the tissue surrounding implants after total joint replacement is closely associated with the innate immune response to surgical implants. Wear particles are known to increase apoptosis and impair the innate immunity in macrophages, which can cause immunosuppression around the implants. Excessive autophagy can induce apoptosis. However, the link between autophagy and apoptosis in macrophages during chronic inflammation and infection remains unknown. In this study, we investigated the autophagy and apoptosis induced by titanium particles in RAW264.7 macrophages, and in the interface membrane of patients with late‐onset periprosthetic joint infection (PJI). We found that titanium particles stimulated autophagy and apoptosis in macrophages. Inhibition of autophagy significantly reduced titanium particle‐induced apoptosis in macrophages, which may be related to the PI3K/Akt signaling pathway. The secretion of inflammatory factors, such as IL‐1β, IL‐6, and TNF‐α, decreased after inhibition of autophagy in titanium particle‐stimulated macrophages, which may be caused by immune dysfunction due to titanium particle‐induced autophagy and apoptosis in macrophages. Furthermore, our in vivo mouse calvarial model also showed that autophagy inhibitors lowered the rate of cell apoptosis. Our findings indicate that wear particle‐induced apoptosis may be caused by enhanced autophagy in macrophages, which could potentially impair the local innate immunity in periprosthetic tissues and could be a risk factor for PJI. Based on these results, autophagy modulators may act as a new therapeutic option for PJI.

中文翻译：

---

钛颗粒通过 PI3K/Akt 信号通路促进巨噬细胞的自噬来诱导细胞凋亡。

全关节置换术后植入物周围组织的慢性炎症和感染与对手术植入物的先天免疫反应密切相关。已知磨损颗粒会增加细胞凋亡并损害巨噬细胞的先天免疫，这会导致植入物周围的免疫抑制。过度自噬可诱导细胞凋亡。然而，慢性炎症和感染期间巨噬细胞自噬和凋亡之间的联系仍然未知。在这项研究中，我们研究了钛颗粒在 RAW264.7 巨噬细胞和晚发性假体周围关节感染 (PJI) 患者界面膜中诱导的自噬和凋亡。我们发现钛颗粒刺激巨噬细胞的自噬和凋亡。抑制自噬显着减少了钛颗粒诱导的巨噬细胞凋亡，这可能与 PI3K/Akt 信号通路有关。抑制钛颗粒刺激的巨噬细胞自噬后IL-1β、IL-6和TNF-α等炎症因子的分泌减少，这可能是由于钛颗粒诱导的巨噬细胞自噬和细胞凋亡引起的免疫功能障碍所致。巨噬细胞。此外，我们的体内小鼠颅骨模型还显示自噬抑制剂降低了细胞凋亡率。我们的研究结果表明，磨损颗粒诱导的细胞凋亡可能是由巨噬细胞自噬增强引起的，这可能会损害假体周围组织的局部先天免疫，并可能是 PJI 的危险因素。基于这些结果，