""""""""Role of Inflammation in Pulmonary Injury"""""""" seeks to better understand molecular and cellular mechanisms responsible for pathological inflammation of the lung and consequent myocardial dysfunction. Diapedesis of immune cells is central to the inflammatory process and appears to be regulated differently in the systemic and pulmonary microcirculations. Project by Linden, """"""""Molecular and Cellular Targets of Adenosine in Lung"""""""" focuses on identifying how cytokines and the A2A Adenosine receptor (A2AAR) regulate leukocytes and endothelial cells (EC) and how adenosine inhibits bleomycin-induced pulmonary inflammation. The project and PPG leader, Joel Linden, is an authority on adenosine receptors and adenosine regulation of inflammation and tissue injury. The A2AAR will be selectively deleted from targeted inflammatory cells. Project by Duling, """"""""Neutrophil traffickinq to normal and inflamed lung"""""""" will identify adhesion molecules and cytokines and their receptors that are responsible for regulating leukocyte trafficking to the lung inflamed by aerosolized, intratracheal or systemic LPS. Dr. C. Ed Rose, an expert on the pulmonary response to LPS, will assist Klaus Ley, a leading authority on the regulation of the leukocyte adhesion and diapedesis. Project by French, """"""""Cardiopulmonary Response to Lung Injury"""""""" will investigate the mechanisms by which in situ pulmonary IRI diminishes heart function. Brent French, an expert on the use of magnetic resonance imaging to non-invasively measure myocardial regional wall motion will collaborate with Jurgen Schrader, an authority in magnetic resonance spectroscopy to assess myocardial energetics. The PPG is supported by state-of-the art core facilities: mouse genetics, inflammatory cell trafficking, and quantification of mRNA and protein. The program is well integrated, focusing on common themes of pulmonary inflammation and mechanisms of lung protection by adenosine. These studies will provide new insights into the cells and cytokines that control lung and heart inflammation and injury and is likely to spawn new therapies.
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