DRUG-INDUCED IN-VITRO INHIBITION OF NEUTROPHIL-ENDOTHELIAL CELL-ADHESION

1 Leukocyte-endothelial cell interactions play an important role durin g ischaemia-reperfusion events. Adhesion molecules are specifically im plicated in this interaction process. 2 Since defibrotide has been sho wn to be an efficient drug in reducing damage due to ischaemia-reperfu sion in many experimental models, we analysed the effect of defibrotid e in vitro on leukocyte adhesion to endothelial cells in basal conditi ons and after their stimulation. 3 In basal conditions, defibrotide (1 000 mu g ml(-1)) partially inhibited leukocyte adhesion to endothelial cells by 17.3%+/-3.6 (P<0.05), and after endothelial cell stimulation (TNF-alpha, 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 mu g ml(-1)) did not demonstrate a significant inhibitory effect whereas use of the monoclonal antibod y anti-LFA-1 (5 mu g ml(-1)) significantly interfered with the effect of defibrotide. 5 This result was confirmed in NIH/3T3-ICAM-1 transfec ted cells. 6 We conclude that defibrotide is able to interfere with le ukocyte adhesion to endothelial cells mainly in activated conditions a nd that the ICAM-1/LFA-1 adhesion system is involved in the defibrotid e mechanism of action.