Secretory immunoglobulin A (sIgA) plays a crucial role in mucosal surface defense. We tested the hypothesis that colonic sIgA secretion is under enteric neural control. Immunohistochemistry of the porcine distal colonic mucosa revealed presumptive cholinergic and adrenergic nerve fibers apposed to secretory component (SC)-positive crypt epithelial cells and neighboring IgA+ plasmacytes. The cholinomimetic drug carbamylcholine elicited rapid, atropine-sensitive IgA secretion into the luminal fluid bathing mucosal explants mounted in Ussing chambers. The adrenergic receptor agonist norepinephrine also increased IgA secretion, an action inhibited by phentolamine. These effects were independent of agonist-induced anion secretion. In Western blots of luminal fluid, both agonists increased the density of protein bands co-immunoreactive for IgA and SC. Mucosal exposure to enterohemorrhagic Escherichia coli did not affect IgA secretion, and carbamylcholine treatment did not affect mucosal adherence of this enteropathogen. Acetylcholine and norepinephrine, acting respectively through muscarinic cholinergic and alpha-adrenergic receptors in the colonic mucosa, stimulate sIgA secretion and may enhance mucosal defense in vivo.
Bibliographical noteFunding Information:
The authors thank Melissa A. Casey and Sarah M. Keupp for excellent technical assistance in some aspects of this investigation. This work was supported in part by National Institutes of Health grants RO1 DA-10200, RO1 MH-50431 and RO1 AI-44918. This article is dedicated to the memory of our colleague Dr. Gary E. Duke (1937–2006), whose research contributions in the field of comparative gastroenterology will be of enduring significance.
- Alpha-adrenergic receptor
- Escherichia coli O157:H7
- Mucosal immunity
- Muscarinic cholinergic receptor
- Secretory component