Cholinergic leukocytes in sepsis and at the neuroimmune junction in the spleen.

International Immunopharmacology
Donald B HooverTammy R Ozment

Abstract

The spleen is a key participant in the pathophysiology of sepsis and inflammatory disease. Many splenocytes exhibit a cholinergic phenotype, but our knowledge regarding their cholinergic biology and how they are affected by sepsis is incomplete. We evaluated effects of acute sepsis on the spleen using the cecal ligation and puncture (CLP) model in C57BL/6 and ChATBAC-eGFP mice. Quantification of cholinergic gene expression showed that choline acetyltransferase and vesicular acetylcholine transporter (VAChT) are present and that VAChT is upregulated in sepsis, suggesting increased capacity for release of acetylcholine (ACh). High affinity choline transporter is not expressed but organic acid transporters are, providing additional mechanisms for release. Flow cytometry studies identified subpopulations of cholinergic T and B cells as well as monocytes/macrophages. Neither abundance nor GFP intensity of cholinergic T cells changed in sepsis, suggesting that ACh synthetic capacity was not altered. Spleens have low acetylcholinesterase activity, and the enzyme is localized primarily in red pulp, characteristics expected to favor cholinergic signaling. For cellular studies, ACh was quantified by mass spectroscopy using d4-ACh interna...Continue Reading

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Citations

May 4, 2021·Frontiers in Immunology·Namrita Halder, Girdhari Lal
Jul 3, 2021·International Journal of Molecular Sciences·Masato MashimoTakeshi Fujii
Aug 7, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Widuri KhoClaudia D Spies
Nov 2, 2021·Frontiers in Neuroscience·Cindy G J CleypoolRonald L A W Bleys

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