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In this ALI model, C5aR expression (protein) was found to occur on upper (bronchial) and lower (alveolar) airway epithelial cells. An adenovirus construct (siRNA) was used to silence mRNA for C5aR in the lung. Under such conditions, C5aR protein was markedly reduced on lung epithelial cells, resulting in much reduced leakage of albumin into the lung, diminished buildup of PMNs, and lower levels of proinflammatory mediators in bronchoalveolar lavage fluids. These studies indicate that bronchial and alveolar epithelial cell C5aR is up\u2010regulated and greatly contributes to inflammation and injury in the lung. The use of siRNA administered into the airways avoids systemic suppression of C5aR, which might compromise innate immunity. It is possible that such an intervention might be employed in humans with ALI or acute respiratory distress syndrome as well as in upper\u2010airway inflammatory diseases, such as chronic obstructive pulmonary disease and asthma, where there is evidence for complement activation and buildup of PMNs.\u2014Sun, L., Guo, R.\u2010F., Gao, H., Sarma, J. V., Zetoune, F. S., Ward, P. A. Attenuation of IgG immune complex\u2010induced acute lung injury by silencing C5aR in lung epithelial cells.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    23, 3808\u20133818 (2009).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.09-133694","type":"journal-article","created":{"date-parts":[[2009,7,20]],"date-time":"2009-07-20T21:09:40Z","timestamp":1248124180000},"page":"3808-3818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Attenuation of IgG immune complex\u2010induced acute lung injury by silencing C5aR in lung epithelial cells"],"prefix":"10.1096","volume":"23","author":[{"given":"Lei","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren-Feng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor Michigan USA"},{"name":"Department of Trauma Surgery Hannover Medical School Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongwei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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