title: Surfactant Proteins SP-A and SP-D Ameliorate Pneumonia Severity and Intestinal Injury in a Murine Model of Staphylococcus Aureus Pneumonia.
abstract: Staphylococcus aureus pneumonia is an important cause of sepsis which causes gut injury, inflammation, and apoptosis. The surfactant proteins surfactant protein A (SP-A) and surfactant protein D (SP-D) bind bacterial pathogens and facilitate clearance of pathogens, apoptotic bodies, and modulate immune responses. SP-A and SP-D are expressed in both lung and gut epithelia. We hypothesize SP-A and SP-D regulate pneumonia severity and gut injury during pneumonia.
  
  
  
  Wild-type (WT) and SP-A and SP-D double knockout (SP-A/D KO) mice were subjected to S. aureus or sham pneumonia. Bronchoalveolar lavage and tissue harvest were performed 24 h later. Pneumonia severity, gut mucosal injury, inflammation, and apoptosis were measured using a combination of histology, immunohistochemistry, cytokine assay, TUNEL assay, quantitative real-time polymerase chain reaction, and Western blot analyses.
  
  
  
  Pneumonia increased gut inflammation, apoptosis, and mucosal injury in both groups. Pneumonia histology and bacterial growth in bronchoalveolar lavage fluid demonstrate more severe infection in SP-A/D KO mice compared with WT controls. SP-A/D KO mice with pneumonia also demonstrate more severe histologic gut mucosal injury, increased gut apoptosis, elevated caspase-3 levels, and Bax/Bcl-2 mRNA expression compared with WT pneumonia mice. Nuclear factor κB (NF-κB) p65 expression and its nuclear translocation, gut levels of tumor necrosis factor α and interleukin-1β were all increased in SP-A/D KO mice with pneumonia compared with WT controls.
  
  
  
  These data provide evidence SP-A and SP-D attenuate S. aureus pneumonia severity resulting in decreased intestinal mucosal injury, apoptosis, and inflammation. Improved pulmonary clearance of S. aureus decreased caspase-3 and Bax/Bcl-2 expressions and decreased activation of the NF-κB signaling pathway in intestine represent potential mechanisms for the effects of SP-A and SP-D on gut injury during pneumonia.
authors: *Department of Surgery, SUNY Upstate Medical University, Syracuse, New York †Department of Emergency Medicine, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Xianjin
authors: X
authors: Du
authors: Qinghe
authors: Q
authors: Meng
authors: Asim
authors: A
authors: Sharif
authors: Osama A
authors: OA
authors: Abdel-Razek
authors: Linlin
authors: L
authors: Zhang
authors: Guirong
authors: G
authors: Wang
authors: Robert N
authors: RN
authors: Cooney
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007422:Intestines / Q000166:cytology / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011023:Pneumonia, Staphylococcal / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D051028:bcl-2-Associated X Protein; D053148:Caspase 3