Department of Physiology, Augusta University, Augusta, GA 30912.
Department of Oral Biology, Augusta University, Augusta, GA 30912.
J Immunol. 2018 May 15;200(10):3568-3586. doi: 10.4049/jimmunol.1701605. Epub 2018 Apr 16.
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.
我们检验了这样一个假设，即口服 NaHCO3 会刺激脾脏的抗炎途径。口服 NaHCO3 后，巨噬细胞向 M2（调节性）表型极化的趋势增强，FOXP3+CD4+T 淋巴细胞在大鼠的脾脏、血液和肾脏中增加。在人类受试者中，口服 NaHCO3 后也观察到类似的巨噬细胞极化抗炎变化。令人惊讶的是，我们发现，在手术剖腹术中（假脾切除术）进行的温和操作以在中线可视化脾脏，足以消除大鼠的反应，并导致包膜间皮细胞的肥大/增生。发现由间皮细胞排列的薄胶原连接与包膜间皮相连。这些连接处的间皮细胞对泛神经元标志物 PGP9.5 和乙酰胆碱酯酶呈阳性染色，并含有许多超微结构元素，这些元素在视觉上类似于神经元结构。脆弱的间皮连接的破坏或迷走神经的横断均导致包膜间皮乙酰胆碱酯酶染色减少和脾脏质量减轻。我们的数据表明，口服 NaHCO3 激活了脾脏的抗炎途径，并提供了证据表明，介导这种反应的信号通过间皮细胞的新型神经元样功能传递到脾脏。
