Summary

Accumulation of platelets might contribute to acute lung injuryduring systemic inflammation. The aim of the study was to elucidatethe role of the poly (ADP-ribose) synthetase, a nucleotide-polymerizising enzyme, in mediation of platelet-endothelialcell interaction through regulation of adhesion molecules withinthe pulmonary microcirculation during endotoxemia. Weused in vivo fluorescence microscopy to quantify kinetics of fluorescentlylabeled erythrocytes and platelets in rabbit pulmo-naryarterioles and venules. Six hours after onset of endotoxininfusion we observed a massive interaction of platelets with themicrovascular endothelial cells, whereas under control conditions,no platelet sequestration was measured. An up-regulation of P- and E-selectin was detected in lung tissue followingendotoxin infusion by immunohistochemistry and Western blotanalysis. Blockade of endothelial P-selectin with fucoidin resultedin a reduction of the endotoxin-induced platelet-endothelialcell interaction. Inhibition of poly (ADP-ribose) synthetase by3-aminobenzamide inhibited the endotoxin-induced expressionof endothelial P- and E-selectin and the subsequent recruitmentof platelets. In summary, we provide first in vivo evidence thatplatelets accumulate in pulmonary microcirculation followingendotoxemia. Poly (ADP-ribose) synthetase seems to mediatethis platelet-endothelial cell interaction via P- and E-selectinexpressed on the surface of microvascular endothelium.