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Although surfactant protein (SP)-D plays a critical role in pulmonary innate immunity and several clinical studies suggest that this protein may be implicated in the pathophysiology of ARDS, little is known regarding the function of SP-D in ARDS. In the present study, we induced indirect lung injury by intraperitoneal injection of LPS and direct lung injury by intratracheal injection of LPS in wild-type and Sftpd\u2212\/\u2212 mice to elucidate the role of SP-D during ALI\/ARDS. Results indicate that pulmonary levels of IL-6 and TNF-\u03b1 were higher in Sftpd\u2212\/\u2212 mice when compared with wild-type mice. However, the magnitude of this difference was 10-fold greater after indirect lung injury compared with direct lung injury. After indirect lung injury, there was a 2-fold increase in the number of pulmonary monocyte\/macrophages in the Sftpd\u2212\/\u2212 mice when compared with wild-type mice, whereas pulmonary neutrophils were not increased. After indirect injury, the concentration of granulocyte-macrophage colony stimulating factor (GM-CSF) was approximately 5-fold greater in Sftpd\u2212\/\u2212 mice than wild-type mice. In contrast, after direct injury, the concentration of GM-CSF was 20-fold less in Sftpd\u2212\/\u2212 mice than wild-type mice. Despite increased inflammatory cells and markers of inflammation, survival in Sftpd\u2212\/\u2212 mice after indirect lung injury was paradoxically increased. In conclusion, these results suggest that SP-D inhibits pulmonary inflammation and migration of peripheral monocyte\/macrophages into the lung through GM-CSF\u2013dependent pathways during indirect lung injury.<\/jats:p>","DOI":"10.1165\/rcmb.2009-0436oc","type":"journal-article","created":{"date-parts":[[2010,7,16]],"date-time":"2010-07-16T22:41:14Z","timestamp":1279320074000},"page":"709-715","source":"Crossref","is-referenced-by-count":42,"title":["Surfactant Protein D Deficiency Increases Lung Injury during Endotoxemia"],"prefix":"10.1093","volume":"44","author":[{"given":"Brooke A.","family":"King","sequence":"first","affiliation":[{"name":"Perinatal Institute, Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Kingma","sequence":"additional","affiliation":[{"name":"Perinatal Institute, Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,5,1]]},"reference":[{"key":"2026030623215659200_bib1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1055\/s-2006-948288","volume":"27","year":"2006","journal-title":"Semin Respir Crit Care Med"},{"key":"2026030623215659200_bib2","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1164\/rccm.200208-966WS","volume":"167","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030623215659200_bib3","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1164\/ajrccm.160.6.9901117","volume":"160","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030623215659200_bib4","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1146\/annurev.physiol.63.1.521","volume":"63","year":"2001","journal-title":"Annu Rev Physiol"},{"key":"2026030623215659200_bib5","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1111\/j.1432-1033.2004.04040.x","volume":"271","year":"2004","journal-title":"Eur J Biochem"},{"key":"2026030623215659200_bib6","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0092-8674(03)00758-X","volume":"115","year":"2003","journal-title":"Cell"},{"key":"2026030623215659200_bib7","doi-asserted-by":"crossref","first-page":"7514","DOI":"10.4049\/jimmunol.166.12.7514","volume":"166","year":"2001","journal-title":"J Immunol"},{"key":"2026030623215659200_bib8","doi-asserted-by":"crossref","first-page":"L697","DOI":"10.1152\/ajplung.2001.281.3.L697","volume":"281","year":"2001","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026030623215659200_bib9","doi-asserted-by":"crossref","first-page":"L552","DOI":"10.1152\/ajplung.00142.2004","volume":"288","year":"2005","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026030623215659200_bib10","doi-asserted-by":"crossref","first-page":"28438","DOI":"10.1074\/jbc.273.43.28438","volume":"273","year":"1998","journal-title":"J Biol Chem"},{"key":"2026030623215659200_bib11","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1378\/chest.07-0864","volume":"132","year":"2007","journal-title":"Chest"},{"key":"2026030623215659200_bib12","first-page":"248S","volume":"117","year":"2000","journal-title":"Chest"},{"key":"2026030623215659200_bib13","doi-asserted-by":"crossref","first-page":"38709","DOI":"10.1074\/jbc.M206200200","volume":"277","year":"2002","journal-title":"J Biol Chem"},{"key":"2026030623215659200_bib14","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1136\/thorax.58.11.983","volume":"58","year":"2003","journal-title":"Thorax"},{"key":"2026030623215659200_bib15","first-page":"218","volume":"133","year":"1986","journal-title":"Am Rev Respir Dis"},{"key":"2026030623215659200_bib16","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1378\/chest.116.6.1709","volume":"116","year":"1999","journal-title":"Chest"},{"key":"2026030623215659200_bib17","doi-asserted-by":"crossref","first-page":"3934","DOI":"10.4049\/jimmunol.165.7.3934","volume":"165","year":"2000","journal-title":"J Immunol"},{"key":"2026030623215659200_bib18","doi-asserted-by":"crossref","first-page":"L861","DOI":"10.1152\/ajplung.00145.2006","volume":"292","year":"2007","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026030623215659200_bib19","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1146\/annurev.physiol.63.1.495","volume":"63","year":"2001","journal-title":"Annu Rev Physiol"},{"key":"2026030623215659200_bib20","first-page":"392","volume":"41","year":"2009","journal-title":"J. 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