Oral NaHCO 3 activates the splenic anti‐inflammatory pathway; evidence vagal efferent signals are transmitted to the spleen via a neuronal like function of mesothelial cells.

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 in the spleen and kidneys of rats, and in the blood of human subjects. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response 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, including synaptic ribbons (the presence of which was confirmed by immunohistochemistry). Both disruption of these fragile connections or transection of the vagal nerves below the diaphragm, resulted in loss of capsular mesothelial acetylcholine esterase staining and a significant reduction in splenic mass, which was not additive. Our data indicate that oral NaHCO 3 activates the cholinergic 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. Support or Funding Information This work was supported by grants to Paul O'Connor (NIH DK099548 and 1P01HL134604) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .