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  • Title: Defibrotide in vitro inhibits neutrophil activation by a Ca++-involving mechanism.
    Author: Di Perri T, Laghi Pasini F, Capecchi PL, Ceccatelli L, Pasqui AL, Orrico A.
    Journal: Int J Tissue React; 1987; 9(5):399-406. PubMed ID: 3667109.
    Abstract:
    Defibrotide, a polydeoxyribonucleotide provided with a pro-fibrinolytic and prostacyclin-like activity, was studied as an inhibitor of polymorphonuclear leucocyte activation in vitro. It was found capable of dose-dependently (1-8 X 10(-5) M) inhibiting FMLP-induced activation, as shown by a decrease of enzyme release and free-radical formation (superoxide anion generation and chemiluminescence). A similar inhibiting activity was observed on A23187-induced activation. An increase in extracellular Ca++ concentration significantly prevented the effect of defibrotide on ionophore stimulation. When PMA was employed as stimulating agent, the drug did not show any inhibiting effect. Finally the pre-treatment of cells with theophylline markedly reduced the inhibition by defibrotide of FMLP- and A23187-dependent activation. Since the stimulation of neutrophils by FMLP and A23187 depends on the increase of cytoplasmic free-calcium availability or extracellular calcium entrance respectively, whereas PMA activation is completely independent from any Ca++ change, the inhibiting effect of defibrotide could be attributed to a Ca++-involving mechanism.
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