Surfactant Proteins SP-A and SP-D Ameliorate Pneumonia Severity and Intestinal Injury in a Murine Model of Staphylococcus Aureus Pneumonia

• Published in: Shock (Augusta, Ga.) Ga.), 2016-08, Vol.46 (2), p.164-172
• Main Authors: Du, Xianjin, Meng, Qinghe, Sharif, Asim, Abdel-Razek, Osama A, Zhang, Linlin, Wang, Guirong, Cooney, Robert N
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - physiology; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Bronchoalveolar Lavage Fluid - microbiology; Caspase 3 - genetics; Caspase 3 - metabolism; Disease Models, Animal; Female; Intestines - cytology; Intestines - immunology; Lung - cytology; Lung - immunology; Male; Mice, Inbred C57BL; Mice, Knockout; Pneumonia, Staphylococcal - genetics; Pneumonia, Staphylococcal - immunology; Pneumonia, Staphylococcal - pathology; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Pulmonary Surfactant-Associated Protein A - genetics; Pulmonary Surfactant-Associated Protein A - metabolism; Pulmonary Surfactant-Associated Protein D - genetics; Pulmonary Surfactant-Associated Protein D - metabolism; Signal Transduction
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/SHK.0000000000000587

ABSTRACTStaphylococcus 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. METHODS: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. RESULTS: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. CONCLUSIONS: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.