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

Abstract

We tested the hypothesis that oral NaHCO intake stimulates splenic anti-inflammatory pathways. Following oral NaHCO loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes, and FOXP3CD4 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 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 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.

The therapeutic importance of acid-base balance

“…Several paradigms have been proposed to suppress a pathological immune response. Oral NaHCO 3 dosing in rats stimulates an anti-inflammatory response; this effect could be harnessed to prevent tissue damage in autoimmune diseases such as rheumatoid arthritis [336] . One preliminary study in mice even suggests that oral NaHCO 3 dosing could be useful to suppress peanut allergy [337] .…”

Inflammatory macrophages in the kidney contribute to salt-sensitive hypertension

“…They demonstrated that alongside the progressive increase in blood pressure and histological renal injury, there was a continual increase in renal macrophages, clearly demonstrating sustained innate immune system activation in the kidney. A recent study by Ray et al (31) demonstrated that the macrophage polarization in the kidneys of Dahl SS rats on a high-salt diet can be shifted from an M1 phenotype toward an M2 phenotype by oral sodium bicarbonate intake.…”

Acidosis, cognitive dysfunction and motor impairments in patients with kidney disease

“…The effects of extracellular acidosis on immune cells have been covered by multiple studies [ 39 ], but except for indirect associations, a pH-dependent modulation of the immune response in CKD has not been shown. Oral HCO 3 − supplementation given to a hypertensive kidney disease rat model activated polarization of macrophages to the anti-inflammatory M2 type, suggesting that acidosis might regulate splenic immune responses in CKD [ 40 ].…”