Premium
CO‐releasing molecules modulate leukocyte/endothelial cell adhesion: under static and flow studies
Author(s) -
Urquhart Paula,
Cooper Dianne,
Motterlini Roberto,
Perretti Mauro
Publication year - 2006
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.20.5.a1321-c
Carbon monoxide (CO) is continually produced in the body as a byproduct of heme catabolism, by the action of heme‐oxygenase. At low concentrations CO possesses pleiotropic homeostatic activities including inhibiting platelet aggregation and cytokine production. Recently, a water soluble compound, trycarbonylcholo(glycinato)ruthenium (II) (CORM‐3), has been developed and found capable of releasing CO in physiological medium. CORM‐3 has been shown to be an effective means of transporting and releasing CO in vitro and in vivo . The aim of this study was to investigate the effect of CORM‐3 on endothelial‐leukocyte interactions employing flow cytometry and fluorescence activated cell‐sorting (FACS) techniques. Human umbilical vein endothelial cells (HUVECs) prestimulated for 4 h with 10 ng/ml TNF‐α were superfused with human neutrophils pre‐treated with CORM‐3 (0–10μM). 1μM and 10μM CORM‐3 produced a significant decrease (60 ±5% and 54 ±10% respectively) in cell capture and rolling. To determine a potential target cell for CORM‐3, assays of endothelial and neutrophil cell activation were performed. Whereas CORM‐3 did not modify HUVEC response to TNF‐α (e.g. adhesion molecule expression, prostaglandin or chemokine generation), neutrophil incubation with CORM‐3 produced a dose‐dependent reduction in CD11b up‐regulation. This study sheds light on specific anti‐inflammatory properties of CO and highlights a selective effect on leukocyte/endothelial cell interaction. This work is supported by the British Heart Foundation.