Summary
Enolase-1 (ENO1) is a ‘moonlighting protein’ with multiple functions. When expressed on the cell surface, ENO1 binds plasminogen (PLG) and facilitates cell migration via plasmin (PLM)-mediated lysis of extracellular matrix proteins. Here, we observed that ENO1 expression on the neutrophil surface was markedly increased upon inflammatory stimulation both in vitro and in vivo. An anti-ENO1 monoclonal antibody (mAb), 7E5, which blocks ENO1-PLG interaction, effectively suppressed the fibrinolytic activity of inflammatory neutrophils. In mouse models of acute inflammation, including lipopolysaccharide (LPS)-induced lung injury and necrotic cell challenge, the 7E5 mAb significantly reduced neutrophil recruitment and the formation of neutrophil extracellular traps (NETs). Furthermore, 7E5 neutralized the immunostimulatory activity of soluble ENO1 protein, which was substantially elevated in the circulation of animals during acute inflammation. These findings suggest that ENO1 plays a crucial role in triggering inflammation and mediating neutrophil infiltration. Targeting ENO1 using antibodies could represent a promising strategy to mitigate tissue damage caused by excessive neutrophilic inflammation.
Competing Interest Statement
The authors have declared no competing interest.