Abstract
Abstract Defibrotide (a polydeox-yribonucleotide) and oligotide (an oligodeoxyribonucleotide) obtained from mammalian single-stranded DNA, have been demonstrated to have anti-ischemic activity in some experimental models of ischemia/ reperfusion of kidney in rats. We hypothesized that their anti-is chemic activity could be related to an inhibition of leukocyte-endothe lial cell adhesion and also the con sequent generation of oxygen free radicals by leukocytes. We studied the in vitro adhesion of neutrophils to human umbilical vein endothelial cells under basal conditions and following neutrophil or endothelial cell activation (using 10--7 fMLP and SO0 U/ml TNF-α, respectively). De fibrotide and oligotide significantly inhibited neutrophil adhesion to endothelial cells (after only 1 min of drug treatment). When the anti-LFA-1 70H12 F(ab)2 monoclonal antibody was used, the drugs exerted only slight additional inhibition of the adhesion of fMLP-acti-vated neutrophils to endothelium. These results, confirmed in NIH/ 3T3–ICAM-l-transfected cells, demonstrate that defibrotide and oligo tide interfere with leukocyte adhesion to endothelial cells by an LFA-1–dependent mechanism.
Published Version
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