Dynamic changes and roles of LYVE-1 during lipopolysaccharide-induced ALI/ARDS in mice.

Background: Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) has been recognized as a marker of lymphatic vessels; however, recent studies have reported that LYVE-1 is expressed in diverse cell types and functionally contributes to organ repair. Herein, we examined the expression pattern of LYVE-1 in acute respiratory distress syndrome (ARDS) model mice. Methods: Acute lung injury (ALI) was induced by intratracheal administration of lipopolysaccharide (LPS) in mice. The expression and localization of LYVE-1 during the inflammatory and resolution phases were assessed by immunohistochemistry and western blot analysis. We also assessed the extent of lung injury following pharmacological inhibition of LYVE-1. Results: During the inflammatory phase of lung injury, 6 h after LPS treatment, a marked decrease in LYVE-1 expression was observed, accompanied by the accumulation of hyaluronan in the tissue. During the repair process at 12 and 24 h, LYVE-1 expression transiently increased beyond baseline levels before returning to a steady state. Notably, LYVE-1-positive M2 macrophages were detected during the resolution phase. Furthermore, LYVE-1 inhibition exacerbated the severity of lung injury and resulted in poor prognosis. Conclusion: LYVE-1 exhibits dynamic expression during lung inflammation and repair, not only in lung tissues but also in M2-like macrophages. Therefore, LYVE-1 may serve as a target for future pharmacological interventions in ALI.