Abstract Objective Severe hypothermia can precipitate acute lung injury (ALI) and may progress to acute respiratory distress syndrome (ARDS). Alveolar macrophage (AM) polarization plays a pivotal role in both the pathogenesis and resolution of ALI/ARDS. This study aimed to investigate alterations in AM polarization and to identify potential regulatory targets of macrophage polarization in severe hypothermia-induced ALI (SH-ALI). Methods An SH-ALI rat model was established by immersion in 15 °C seawater for 5 h. Survival rate, inflammatory cytokine levels, lung histopathology, lung wet-to-dry weight ratio, and AM polarization status were assessed. RNA sequencing was performed to identify differentially expressed genes in bronchoalveolar lavage fluid-stimulated AMs from SH-ALI rats compared with normal AMs. Lipocalin-2 (LCN2) was identified and validated as a differentially expressed gene in SH-ALI. The effects of LCN2 on macrophage polarization, survival rate, lung injury severity, and inflammatory factor levels were further evaluated. Results SH-ALI was characterized by increased mortality, elevated inflammatory cytokine levels, marked inflammatory cell infiltration, aggravated pulmonary edema, and significant pulmonary parenchyma injury. An imbalance between M1 and M2 macrophage polarization was observed, with severe hypothermia promoting M1 polarization. LCN2 expression was significantly upregulated in SH-ALI rats. Downregulation of LCN2 suppressed M1 polarization and alleviated lung injury in SH-ALI in rats. Conclusion Immersion in 15 °C seawater for 5 h successfully establishes an SH-ALI rat model. SH-ALI is associated with excessive M1 polarization, and LCN2 knockdown mitigates lung injury by inhibiting M1 polarization in SH-ALI rats.
Zheng et al. (Sat,) studied this question.