Oral NaHCO3 Activates a Splenic Anti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells

  • Sarah C. Ray
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Babak Baban
    †Department of Oral Biology, Augusta University, Augusta, GA 30912;
  • Matthew A. Tucker
    ‡Georgia Prevention Institute, Augusta University, Augusta, GA 30912; and
  • Alec J. Seaton
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Kyu Chul Chang
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Elinor C. Mannon
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Jingping Sun
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Bansari Patel
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Katie Wilson
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Jacqueline B. Musall
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Hiram Ocasio
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Debra Irsik
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Jessica A. Filosa
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Jennifer C. Sullivan
    *Department of Physiology, Augusta University, Augusta, GA 30912;
  • Brendan Marshall
    §Department of Cell Biology and Anatomy, Augusta University, Augusta, GA 30912
  • Ryan A. Harris
    ‡Georgia Prevention Institute, Augusta University, Augusta, GA 30912; and
  • Paul M. O’Connor
    *Department of Physiology, Augusta University, Augusta, GA 30912;

抄録

<jats:title>Abstract</jats:title> <jats:p>We tested the hypothesis that oral NaHCO3 intake stimulates splenic anti-inflammatory pathways. Following oral NaHCO3 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 NaHCO3 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 NaHCO3 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.</jats:p>

収録刊行物

  • The Journal of Immunology

    The Journal of Immunology 200 (10), 3568-3586, 2018-05-15

    The American Association of Immunologists

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