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A new carbon monoxide (CO)‐releasing molecule (CORM401) suppresses PMN migratory potential through an F‐actin‐dependent mechanism
Author(s) -
Inoue Ken,
Patterson Eric,
Chung Kyukwang,
Potter Richard F,
Capretta Alfredo,
Fraser Douglas D,
Cepinskas Gediminas
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.723.5
Subject(s) - chemotaxis , phosphorylation , actin , chemistry , biophysics , flow cytometry , microbiology and biotechnology , carbon monoxide , biochemistry , receptor , biology , catalysis
Background Our previous work suggested that a newly synthesized Mn 2+ ‐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. Methods Freshly 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. Results Pre‐treating PMN with CORM401 significantly reduced their directionality and mean velocity (p<0.01) in response to fMLP compared to controls. CORM401 significantly reduced F‐actin polymerization in fMLP‐stimulated PMN (p<0.01). Pre‐treating PMN with CORM401 did not result in decreased MAPK phosphorylation, but resulted in decreased PAK phosphorylation (p<0.05). Conclusion CORM401 suppresses neutrophil migratory potential through an F‐actin‐dependent mechanisms. This study showed for the first time that the use of CORM401 has an effect on F‐actin‐dependent mechanisms of PMN. Support or Funding Information HSFO 393, IRF‐25‐12