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Protection of the Pulmonary Vascular Endothelium

$250,168R01FY2003HLNIH

University Of Virginia Charlottesville, Charlottesville VA

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Abstract

DESCRIPTION (provided by applicant): This proposal examines the role of neutrophils, lung-resident macrophages, and nitric oxide in pulmonary ischemia reperfusion (I/R) injury. Three specific hypotheses will be tested. (1) pulmonary macrophages play a major role in lung I/R injury, and this injury is increased by a relative lack of NO which normally suppresses macrophage cytokine production; (2) Activation of adenosine 2A (A2A) receptors can substantially reduce lung I/R injury; the role of NO in mediating the biological effects of A2A receptor activation in lung I/R injury will be studied; (3) reperfusion injury increases the risk of subsequent acute and chronic rejection. Studies to test these hypotheses will be performed in a blood-perfused rabbit lung model of I/R, a rat model of lung I/R injury, a mouse isolated lung I/R model, and a porcine lung transplantation model.

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Protection of the Pulmonary Vascular Endothelium · GrantIndex