Abstract
Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks in DNA, plays an important role in the tissue injury associated with ischaemia–reperfusion injury and inflammation. The aim of the present study was to evaluate the effects of a novel and potent inhibitor of PARP activity on neutrophil recruitment in the acute inflammation induced by zymosan-activated plasma. Intra-thoracic administration of zymosan-activated plasma leads to an increase in neutrophil infiltration of the lung at 24 hr. The potent PARP inhibitor 5-aminoisoquinolinone (5-AIQ) reduced the degree of lung injury and attenuated the expression of P-selectin and ICAM-1 as well as the recruitment of neutrophils into the injured lung. The up-regulation/expression of P-selectin and ICAM-1 in human endothelial cells exposed to oxidative stress (peroxynitrite) or to a pro-inflammatory cytokine (tumor necrosis factor α, TNFα) was also attenuated by 5-AIQ. These findings provide the first evidence that the activation of PARS participates in neutrophil-mediated lung injury by regulating the expression of P-selectin and ICAM-1.
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