Background: Macrophages secrete IL-1? in acute lung injury. OMVs are vesicles shed by Gram-negative bacteria and contain more LPS. Secretory autophagy is a process where autophagosomes directly bind to the cell membrane to release intracellular substances. GBP2 promotes the rupture of pathogen-containing vacuoles and can activate NLPR3 inflammasome. However, whether IL-1? is also secreted through secretory autophagy in acute lung injury, and whether GBP2 is involved in it are still unclear.

Aims: We hypothesized that OMV promotes secretory autophagy of IL-1? in macrophage during acute lung injury via GBP2.

Methods: In vivo, we evaluated the degree of acute lung injury caused by OMV and the secretion level of IL-1? in BALF of 6-8-week-old mice; In vitro, RAW264.7 was stimulated with OMV to detect the level of secretory autophagy, lysosomal function and IL-1?. Changing the expression of GBP2 and key proteins of secretory autophagy, then detect the IL-1? secretion, the proteins of secretory autophagy and lysosomal activity

Results: In vivo, OMV led to acute lung injury in mice, increasing the level of IL-1? in BALF and the key autophagic molecule LC3 ; In vitro, OMV stimulated RAW264.7 to increase IL-1?, raising the expression of secretory autophagy and GBP2, while decreasing the lysosomal activity. Decresing the level of GBP2 can reverse the increment caused by OMV stimulation. After applying lysosomal inhibitor, the secretion of IL-1? decreased significantly.

Conclusion: OMV enhances the secretory autophagy process by promoting the expression of GBP2, which further uplifts the secretion of IL-1? in macrophage.