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Ischemia-reperfusion injury is one of the main causes of primary graft dysfunction after lung transplantation. Fas-mediated apoptosis plays a major role in the pathogenesis of ischemia-reperfusion injury. Exogenous administration of small interfering RNA (siRNA) is an effective strategy to specifically silence the expression of proteins through blocking the translation of mRNA. The aim of this study was to investigate in an ex vivo mouse model of lung ventilation and perfusion whether a specific siRNA targeting Fas is able to reduce ischemia-reperfusion injury.

Ventilator-induced lung injury is characterized by release of inflammatory mediators and increased vascular permeability resulting in alveolar edema formation. Thrombopoietin (TPO), whose most known function is the stimulation of the proliferation of megakaryocytes, has also shown several proinflammatory effects. Moreover, TPO receptor, c-Mpl, is constitutively expressed on endothelial cells and may modulate the permeability of the endothelium. We investigated the role of TPO in the impairment of the alveolar-capillary membrane resulting in alveolar edema formation during mechanical ventilation.