Rab32-mediated macrophage apoptosis and apoptotic body release promote M1 polarization in ARDS via the Cxcl11/Ccl4/NF-κB pathway.

Acute respiratory distress syndrome (ARDS) is a critical condition characterized by diffuse alveolar injury, often precipitated by infections, trauma, and other etiological factors, and is associated with a high mortality rate. ARDS induced by serious infections is particularly challenging to manage, as the administration of antibiotics, while essential for infection control, is insufficient to mitigate the associated inflammation, thereby contributing to elevated mortality and intubation rates. Despite extensive research, the precise pathophysiological mechanisms underlying ARDS remain poorly understood. A key factor influencing the prognosis of ARDS is the polarization of alveolar macrophages. In this study, we demonstrated that high-concentration lipopolysaccharide (LPS) not only directly induces M1 macrophage polarization but also triggers macrophage apoptosis via Rab32 activation. Furthermore, the Apoptotic bodies (ABs) released by M1-macrophages exacerbated the inflammatory response by influencing neighboring macrophages through the Cxcl11/Ccl4/NF-κB signaling pathway, thereby aggravating the M1/M2 ratio imbalance. In conclusion, in addition to rigorous antibiotic therapy, targeting M1 macrophage apoptosis inhibition may represent a crucial therapeutic strategy for improving the clinical outcomes and survival rates of ARDS patients.