A new carbon monoxide (CO)-releasing molecule (CORM401) suppresses PMN migratory potential through an F-actin-dependent mechanism

BackgroundOur previous work suggested that a newly synthesized Mn2+-based water-soluble carbon monoxide (CO)-releasing molecules (CORM401) interfered with PMN recruitment by inhibiting transendothelial migration across the endothelium. In this study, we further investigated the effects of CORM401 on PMN chemotaxis by an F-actin-dependent mechanism. MethodsFreshly isolated human PMN were placed into a μ-Slide chemotaxis chamber and allowed to migrate in response to an fMLP (10μM) gradient for 50 min in the absence or presence of 100 μM CORM401 or inactive CORM401(iCORM401). PMN migration was recorded and analyzed for migration directionality and velocity. To assess the effect of CORM401 on fMLP-stimulated PMN function, F-actin polymerization was measured by flow cytometry. In addition, the phosphorylation of MAPK and p21-activated kinases (PAK) in PMN were examined by immunoblotting. ResultsPre-treating PMN with CORM401 significantly reduced their directionality and mean velocity (p<0.01) in response to fM...