Abstract
Defibrotide (a polydeoxyribonucleotide) 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-ischemic activity could be related to an inhibition of leukocyte-endothelial cell adhesion and also the consequent 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 500 U/ml TNF-α, respectively). Defibrotide 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-activated neutrophils to endothelium. These results, confirmed in NIH/3T3-ICAM-1-transfected cells, demonstrate that defibrotide and oligotide interfere with leukocyte adhesion to endothelial cells by an LFA-1-dependent mechanism.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Baumann H, Gauldie J (1994) The acute phase response. Immunol Today 15: 74–80
Bevilacqua MP, Pober JS, Wheeler ME, Cotran RS, Gibrone MA Jr (1985) In terleukin 1 acts on cultured human vas cular endothelium to increase the adhe sion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest 76: 2003–2011
Boyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 297: 77–89
Ferrero ME, Mami A, Parise M, Salari PC, Gaja G (1991) Protection of rat heart from damage due to ischemia-reperfusion during procurement and grafting by defibrotide. Transplantation 52: 611–615
Hansen PR (1995) Role of neutrophils in myocardial ischemia and reperfusion. Circulation 91: 1872–1885
Jaffe EA (ed) (1984) Biology of endothelial cells. Martinus Nijhoff, Boston
Mami A, Ferrero ME, Rovati M, Salari PC, Gaja G (1990) Protection of kidney from postischemic reperfusion injury in rats treated with defibrotide. Transplant Proc 22: 2226–2229
Miwa S, Kawasaki S, Makuuchi M, Miyasaka M, Yamazaki S, Sekiguchi M, Isobe M (1995) Role of ICAM-1 and LFA-1 in a cardiac xenograft rejection model. Transplant Proc 27: 111–112
Parham P (1983) On the fragmentation of monoclonal IgG1, IgG2a, and IgG2b form BALB/c mice. J Immunol 131: 2895–2902
Patel KD, Zimmerman GA, Prescott SM, McEver RP, McIntyre TM (1991) Oxygen radicals induce human endothelial cells to express GMP-140 and bind neutrophils. J Cell Biol 112: 749–759
Simpson PJ, Todd RF III, Mickelson JK, Fantone JC, Gallagher KP, Lee KA, Tamura Y, Cronin M, Lucchesi BR (1990) Sustained limitation of myocardial reperfusion injury by a monoclonal antibody that alters leukocyte function. Circulation 81: 226–237
Tanaka Y, Albelda SM, Horgan KJ, van Seventer GA, Shimizu Y, Newman W, Hallam J, Newman PJ, Buck CA, Shaw S (1992) CD31 expressed on distinctive T cell subsets is a preferential amplifier of ‘31 integrin-mediated adhesion. J Exp Med 176: 245–253
Varani J, Ginsburg I, Schuger L, Gibbs DF, Bromberg J, Johnson KJ, Ryan US, Ward PA (1989) Endothelial cell killing by neutrophils: synergistic interaction of oxygen radical products and proteases. Am J Pathol 135: 435–438
Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320: 365–376
Weyrich AS, Ma X-L, Lefer DJ, Albertine KH, Lefer AM (1993) In vivo neutralization of P-selectin protects feline heart and endothelium in myocardial ischemia and reperfusion injury. J Clin Invest 91: 2620–2629
Yoshida N, Granger DN, Anderson DC, Rothlein R, Lane C, Kvietys PR (1992) Anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells. Am J Physiol 262: H1891 - H1898
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Pellegatta, F., Ferrero, E., Marni, A., Chierchia, S., Forti, D., Ferrero, M.E. (1996). The anti-ischemic drugs defibrotide and oligotide analogously inhibit leukocyte-endothelial cell adhesion in vitro. In: Mühlbacher, F., et al. Transplant International . Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-00818-8_101
Download citation
DOI: https://doi.org/10.1007/978-3-662-00818-8_101
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-61024-3
Online ISBN: 978-3-662-00818-8
eBook Packages: Springer Book Archive