Autonomic neurotransmitters modulate immunoglobulin A secretion in porcine colonic mucosa

Abstract

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.

The Central Nervous System Modulates the Immune Response to Salmonella

“…The CNS can modulate the activity of the autonomic nervous system (the adrenergic and cholinergic nervous system) and evoke the neuronal release of norepinephrine (NE), acetylcholine (ACh) and other neurotransmitters in peripheral tissues, including the intestinal mucosa (Felten, Felten et al 1987;Kulkarni-Narla, Beitz et al 1999;Kohm and Sanders 2001;Tracey 2002;Green, Lyte et al 2003;Pavlov, Wang et al 2003;Sternberg 2006;Sanders and Kavelaars 2007;Schmidt, Xie et al 2007;Chrousos 2009;Kvetnansky, Sabban et al 2009). These mediators may influence the function of the intestinal mucosa and its associated surface bacterial populations.…”

“…However, little is known about the neuroendocrine regulation of intestinal IgA (Schmidt, Eriksen et al 1999;Schmidt, Xie et al 2007;Reyna-Garfias, Miliar et al 2010).…”

“…Although the intestinal tract is a major site for mucosal immunity and is extensively innervated, little is known about the adrenergic regulation of enteric S-IgA secretion.Norepinephrine stimulates S-IgA secretion by acting through alpha-adrenergic receptors in the colonic mucosa, and in this way may enhance mucosal defense in vivo (Schmidt, Xie et al 2007)]. This neurotransmitter also significantly increases pIgR mRNA expression and intestinal IgA concentration (Reyna-Garfias, Miliar et al 2010).…”

“…Some data indicate that intestinal secretion of immunoglobulin A is stimulated by the muscarinic effect of cholinergic agonists, which suggest that the basal secretion of immunoglobulin A may be influenced by the parasympathetic nervous system (Wilson, Soltis et al 1982;Freier, Eran et al 1987;Freier, Eran et al 1989;Schmidt, Xie et al 2007). However, there is no information about the role of the parasympathetic nervous system in the secretion of IgA during infections by Salmonella.…”

Food fight! Parenteral nutrition, enteral stimulation and gut-derived mucosal immunity

“…Schmidt et al showed that exogenous administration of catecholamines to ex vivo constructs of polarized pig intestinal tissue caused significantly more IgA to be secreted into the apical supernatant. 97 Whether this effect was direct, or mediated by some other secondary signal (like a cytokine) is unknown.…”