Oral NaHCO 3 activates a splenic anti-inflammatory pathway: Evidence that cholinergic signals are transmitted via mesothelial cells

Sarah C. Ray, Babak Baban, Matthew A. Tucker, Alec J. Seaton, Kyu Chul Chang, Elinor C. Mannon, Jingping Sun, Bansari Patel, Katie Wilson, Jacqueline B. Musall, Hiram Ocasio, Debra Irsik, Jessica A. Filosa, Jennifer C. Sullivan, Brendan Marshall, Ryan A. Harris, Paul M. O’Connor

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

We tested the hypothesis that oral NaHCO 3 intake stimulates splenic anti-inflammatory pathways. Following oral NaHCO 3 loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes, and FOXP3 + CD4 + T-lymphocytes increased in the spleen, blood, and kidneys of rats. Similar anti-inflammatory changes in macrophage polarization were observed in the blood of human subjects following NaHCO 3 ingestion. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response in rats and resulted in hypertrophy/hyperplasia of the capsular mesothelial cells. Thin collagenous connections lined by mesothelial cells were found to connect to the capsular mesothelium. Mesothelial cells in these connections stained positive for the pan-neuronal marker PGP9.5 and acetylcholine esterase and contained many ultrastructural elements, which visually resembled neuronal structures. Both disruption of the fragile mesothelial connections or transection of the vagal nerves resulted in the loss of capsular mesothelial acetylcholine esterase staining and reduced splenic mass. Our data indicate that oral NaHCO 3 activates a splenic anti-inflammatory pathway and provides evidence that the signals that mediate this response are transmitted to the spleen via a novel neuronal-like function of mesothelial cells.

Original languageEnglish (US)
Pages (from-to)3568-3586
Number of pages19
JournalJournal of Immunology
Volume200
Issue number10
DOIs
Publication statusPublished - May 15 2018

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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