Drug‐induced in vitro inhibition of neutrophil‐endothelial cell adhesion

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Abstract
1 Leukocyte-endothelial cell interactions play an important role during ischaemia-reperfusion events. Adhesion molecules are specifically implicated in this interaction process. 2 Since defibrotide has been shown to be an efficient drug in reducing damage due to ischaemia-reperfusion in many experimental models, we analysed the effect of defibrotide in vitro on leukocyte adhesion to endothelial cells in basal conditions and after their stimulation. 3 In basal conditions, defibrotide (1000 μg ml−1) partially inhibited leukocyte adhesion to endothelial cells by 17.3% ± 3.6 (P < 0.05), and after endothelial cell stimulation (TNF-α, 500 u ml−1) or after leukocyte stimulation (fMLP, 10−7 m), it inhibited leukocyte adhesion by 26.5% ± 3.4 and 32.4% ± 1.8, respectively (P < 0.05). 4 In adhesion blockage experiments, the use of the monoclonal anntibody anti-CD31 (5 μg ml−1) did not demonstrate a significant inhibitory effect whereas use of the monoclonal antibody anti-LFA-1 (5 μg ml−1) significantly interfered with the effect of defibrotide. 5 This result was confirmed in NIH/3T3-ICAM-1 transfected cells. 6 We conclude that defibrotide is able to interfere with leukocyte adhesion to endothelial cells mainly in activated conditions and that the ICAM-1/LFA-1 adhesion system is involved in the defibrotide mechanism of action.