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Extrapulmonary Expression of Surfactant Protein D and Modulation of the Gut Microbiome
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A2774 - Extrapulmonary Expression of Surfactant Protein D and Modulation of the Gut Microbiome
Author Block: A. Arciniegas1, J. A. Englert2, R. M. Baron1; 1Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, United States, 2Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
BACKGROUND: Surfactant Protein D (SPD) is a collectin protein that plays an important role in innate immunity and host defense. SPD is produced by lung alveolar type II cells, and it has been reported to be produced by other mucosal surfaces. We unexpectedly found that SPD Knockout (KO) mice have increased survival compared to wild type (WT) mice following polymicrobial sepsis (cecal ligation and puncture, CLP) and absence of E. coli in their gut microbiome, in contrast to WT mice that are colonized with E. Coli and become bacteremic with this organism after CLP. Furthermore, administration of recombinant SPD to SPD KO mice permitted retention of E. Coli in the cecum. Localization of SPD expression in the gut has been difficult to discern, and we therefore set out to test the hypothesis that SPD expression in the cecum plays an important role in regulating the microbiome and response to polymicrobial sepsis.
METHODS: WT and SPD KO mice were were subjected to CLP (23g, 1 hole, 50% ligation) or sham laparotomy control. Gastrointestinal tract segments (including esophagus, stomach, duodenum, ileum, jejunum, cecum, colon), lung, pancreas, and kidney were harvested from each mouse for RNA isolation, and SPD gene expression was analyzed using quantitative PCR. Additionally, tissues were formalin fixed and paraffin embedded for future studies using in situ hybridization (RNAscope) for detection of SPD.
RESULTS: In WT mice, as anticipated, SPD was highly expressed in the lung at baseline and after CLP. In the gastrointestinal tract, SPD message was detected only in the duodenum and stomach at baseline at substantial levels. Interestingly, 24hrs post CLP, significant induction of SPD expression was observed in the cecum, as well as in the kidney, of WT mice, while levels of expression in the duodenum were substantially reduced compared with baseline levels.
CONCLUSION: SPD gene expression was found in WT control mice in upper segments of the gastrointestinal tract at baseline and was induced in the cecum after sepsis. Changes in gut SPD expression may play an important role in regulation of the gut microbiome and response to sepsis. Further studies to discern SPD localization in the gut are ongoing.
Author Block: A. Arciniegas1, J. A. Englert2, R. M. Baron1; 1Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, United States, 2Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
BACKGROUND: Surfactant Protein D (SPD) is a collectin protein that plays an important role in innate immunity and host defense. SPD is produced by lung alveolar type II cells, and it has been reported to be produced by other mucosal surfaces. We unexpectedly found that SPD Knockout (KO) mice have increased survival compared to wild type (WT) mice following polymicrobial sepsis (cecal ligation and puncture, CLP) and absence of E. coli in their gut microbiome, in contrast to WT mice that are colonized with E. Coli and become bacteremic with this organism after CLP. Furthermore, administration of recombinant SPD to SPD KO mice permitted retention of E. Coli in the cecum. Localization of SPD expression in the gut has been difficult to discern, and we therefore set out to test the hypothesis that SPD expression in the cecum plays an important role in regulating the microbiome and response to polymicrobial sepsis.
METHODS: WT and SPD KO mice were were subjected to CLP (23g, 1 hole, 50% ligation) or sham laparotomy control. Gastrointestinal tract segments (including esophagus, stomach, duodenum, ileum, jejunum, cecum, colon), lung, pancreas, and kidney were harvested from each mouse for RNA isolation, and SPD gene expression was analyzed using quantitative PCR. Additionally, tissues were formalin fixed and paraffin embedded for future studies using in situ hybridization (RNAscope) for detection of SPD.
RESULTS: In WT mice, as anticipated, SPD was highly expressed in the lung at baseline and after CLP. In the gastrointestinal tract, SPD message was detected only in the duodenum and stomach at baseline at substantial levels. Interestingly, 24hrs post CLP, significant induction of SPD expression was observed in the cecum, as well as in the kidney, of WT mice, while levels of expression in the duodenum were substantially reduced compared with baseline levels.
CONCLUSION: SPD gene expression was found in WT control mice in upper segments of the gastrointestinal tract at baseline and was induced in the cecum after sepsis. Changes in gut SPD expression may play an important role in regulation of the gut microbiome and response to sepsis. Further studies to discern SPD localization in the gut are ongoing.
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