Modulating Neutrophil‐Derived MPO‐Endothelial Surface Binding with CORMs

Abstract

Myeloperoxidase (MPO) binds to vascular endothelial cells (EC) through a mechanism that, at least in part, involves interactions with glycosaminoglycans expressed on the endothelial surface. MPO that is closely associated with endothelial cells can directly damage them through its catalytic activity. Our previous work demonstrated that carbon monoxide‐releasing molecule 3 (CORM‐3) inhibits MPO catalytic activity and can thereby mitigate its detrimental effects during severe inflammation. The effects and mechanisms of CORM‐dependent modulation of MPO‐vascular EC binding are not yet investigated.We have employed in vitro assays to study neutrophil‐derived MPO binding to human umbilical vein EC (HUVEC) following treatment with two structurally different CORMs; CORM‐3 and CORM‐401, synthesized based on Ru or Mn transition metals, respectively.Our results indicate that at equimolar concentrations CORM‐3, but not CORM‐401 inhibits MPO‐endothelial surface binding. Inactivated CORM‐3 (iCORM‐3) did not inhibit MPO binding to ECWe conclude that in addition to CORM‐3‐dependent suppression of MPO catalytic activity, reduced MPO binding to EC in the presence of CORM‐3 may provide an additional mechanism that contributes to CORM‐dependent suppression of inflammation and endothelial damage.