Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100037, PR China.
Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100037, PR China.
Respir Physiol Neurobiol. 2024 Feb;320:104203. doi: 10.1016/j.resp.2023.104203. Epub 2023 Dec 14.
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.
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.
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.
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.
急性肺损伤（ALI）涉及严重的肺损伤和呼吸衰竭，同时伴有肺泡巨噬细胞（AM）的激活。本文旨在验证 paralemmin-3（PALM3）对 ALI 中肺泡巨噬细胞（AM）极化的影响及其作用机制。
通过连续的脂多糖（LPS）吸入建立 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。
PALM3 过表达增加了 ALI 大鼠的死亡率，加重了肺病理损伤，并促进了 AM 向 M1 细胞的极化。相反，PALM3 敲低则产生相反的效果。机制上，PALM3 可能通过作为衔接蛋白促进 Notch 信号转导来促进 M1 极化。
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 的治疗提供新的思路。
