Background

Acute lung injury (ALI) involves severe lung damage and respiratory failure, which are accompanied by alveolar macrophage (AM) activation. The aim of this article is to verify the influence of paralemmin-3 (PALM3) on alveolar macrophage (AM) polarization in ALI and the underlying mechanism of action.

Methods

An ALI rat model was established by successive lipopolysaccharide (LPS) inhalations. The influence of PALM3 on the survival rate, severity of lung injury, and macrophage polarization was analyzed. Furthermore, we explored the underlying mechanism of PALM3 in regulating macrophage polarization.

Results

PALM3 overexpression increased mortality of ALI rats, augmented lung pathological damage, and promoted AM polarization toward M1 cells. Conversely, PALM3 knockdown had the opposite effects. Mechanistically, PALM3 might promote M1 polarization by acting as an adaptor to facilitate transduction of Notch signaling.

Conclusion

PALM3 aggravates lung injury and induces macrophage polarization toward M1 cells by activating the Notch signaling pathway in LPS-induced ALI, which may shed light on ALI/ARDS treatments.

中文翻译：

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Paralemmin-3 通过 Notch 信号通路通过 M1 巨噬细胞极化增强脂多糖诱导的急性肺损伤

背景

急性肺损伤（ALI）涉及严重的肺损伤和呼吸衰竭，并伴有肺泡巨噬细胞（AM）激活。本文的目的是验证 paralemmin-3 (PALM3) 对 ALI 中肺泡巨噬细胞 (AM) 极化的影响及其潜在作用机制。

方法

通过连续吸入脂多糖（LPS）建立ALI大鼠模型。分析PALM3对存活率、肺损伤严重程度和巨噬细胞极化的影响。此外，我们还探讨了 PALM3 调节巨噬细胞极化的潜在机制。

结果

PALM3 过度表达增加了 ALI 大鼠的死亡率，加剧了肺部病理损伤，并促进 AM 向 M1 细胞极化。相反，PALM3 敲低则产生相反的效果。从机制上讲，PALM3 可能通过充当适配器促进 Notch 信号转导来促进 M1 极化。

结论

PALM3 通过激活 LPS 诱导的 ALI 中的 Notch 信号通路，加重肺损伤并诱导巨噬细胞向 M1 细胞极化，这可能为 ALI/ARDS 治疗提供线索。