Schmidt Lisa D, Xie Yonghong, Lyte Mark, Vulchanova Lucy, Brown David R
Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Avenue, St. Paul, Minnesota 55108-6010, USA.
J Neuroimmunol. 2007 Apr;185(1-2):20-8. doi: 10.1016/j.jneuroim.2006.10.028. Epub 2007 Feb 21.
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.
分泌型免疫球蛋白A(sIgA)在黏膜表面防御中起关键作用。我们检验了结肠sIgA分泌受肠神经控制这一假说。猪远端结肠黏膜的免疫组织化学显示,假定的胆碱能和肾上腺素能神经纤维与分泌成分(SC)阳性的隐窝上皮细胞及相邻的IgA(+)浆细胞相邻。拟胆碱药物氨甲酰胆碱促使IgA快速分泌到置于尤斯灌流小室中的黏膜外植体周围的腔内液体中,该作用对阿托品敏感。肾上腺素能受体激动剂去甲肾上腺素也增加IgA分泌,这一作用被酚妥拉明抑制。这些效应独立于激动剂诱导的阴离子分泌。在腔内液体的蛋白质免疫印迹中,两种激动剂均增加了与IgA和SC共免疫反应的蛋白条带密度。黏膜暴露于肠出血性大肠杆菌并不影响IgA分泌,氨甲酰胆碱处理也不影响该肠道病原体的黏膜黏附。乙酰胆碱和去甲肾上腺素分别通过结肠黏膜中的毒蕈碱型胆碱能受体和α-肾上腺素能受体发挥作用,刺激sIgA分泌,并可能在体内增强黏膜防御。