title: Surfactant protein D deficiency increases lung injury during endotoxemia.
abstract: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are major causes of acute respiratory failure with high rates of morbidity and mortality. 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(-/-) mice to elucidate the role of SP-D during ALI/ARDS. Results indicate that pulmonary levels of IL-6 and TNF-α were higher in Sftpd(-/-) 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(-/-) 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(-/-) mice than wild-type mice. In contrast, after direct injury, the concentration of GM-CSF was 20-fold less in Sftpd(-/-) mice than wild-type mice. Despite increased inflammatory cells and markers of inflammation, survival in Sftpd(-/-) 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-dependent pathways during indirect lung injury.
authors.affiliation: Perinatal Institute, Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children’s Hospital Medical Center, Ohio 45229-3039, USA.
authors.forename: Brooke A
authors.initials: BA
authors.lastname: King
authors.forename: Paul S
authors.initials: PS
authors.lastname: Kingma
mesh_terms: D000818:Animals; D019446:Endotoxemia / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency*; D012128:Respiratory Distress Syndrome / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D037663:Pulmonary Surfactant-Associated Protein D; D016178:Granulocyte-Macrophage Colony-Stimulating Factor