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

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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.

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.

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