Defibrotide Blocks Neutrophil Activation Through a Calcium-Dependent Pathway

Di Perri and colleagues, writing in the International Journal of Tissue Reactions in 1987, studied how defibrotide — a polydeoxyribonucleotide drug known for its clot-dissolving and blood-vessel-relaxing effects — acts on white blood cells called neutrophils, which play a central role in inflammation.

Working in laboratory cell cultures, the researchers exposed neutrophils to two chemical triggers, FMLP and A23187, that switch the cells on. Defibrotide reduced this activation in a dose-dependent way across a concentration range of 1 to 8 x 10^-5 M, lowering both the release of enzymes from the cells and the production of free radicals (measured as superoxide generation and chemiluminescence, a light-based marker of cell activity). Raising the calcium level outside the cells weakened defibrotide's effect, and a separate chemical, theophylline, also blunted it. When the cells were instead activated with a third compound, PMA, which works independently of calcium, defibrotide had no effect at all.

Because the pattern of results tracked with calcium involvement, the authors conclude that defibrotide dampens neutrophil activation specifically through a calcium-related mechanism. The study is limited to isolated cells in a dish; it says nothing about effects in a living organism, in skin, or at any particular dose in people.