ノイラミニダーゼの亢進は、インテグリンβ2を介した好中球の接着と免疫応答を促進することにより、肺の炎症を増強する

Acute inflammation in lungs is a leading cause of death worldwide with limited treatments. During the development of inflammatory lung diseases, glycosylation is altered and emerges as a potential therapeutic target. Decreased sialylation is a common change of glycosylation. Yet the role of decreased sialylation in the progression of lung inflammation is complex and remains elusive. Here, we examined the role of sialic acids on neutrophils in modulating integrin β2-regulated cell adhesion and immune responses. The removal of sialic acids increased integrin β2-mediated adhesion and immune responses of neutrophils, including cytokine release, ROS production, and NETs formation. In addition, the removal of sialic acids did not alter the ligand-binding affinity of integrin β2 but increased the ligand-binding valency of integrin β2. In inflamed lungs, binding of RAGE, a ligand highly expressed on lung epithelial cells, to integrin β2 facilitated the interaction of neutrophils with lung cells, which was also enhanced after removing sialic acids. Thus, sialic acids negatively regulate the valency of integrin β2 for its ligands and the subsequent neutrophil adhesion and ligand-induced immune responses. Our study suggests a mechanism for which decreased sialylation potentiates inflammation and provides novel insights into the pathogenesis of lung inflammation.