TY - JOUR
T1 - Adrenergic modulation of Escherichia coli O157:H7 adherence to the colonic mucosa
AU - Green, Benedict T.
AU - Lyte, Mark
AU - Chen, Chunsheng
AU - Xie, Yonghong
AU - Casey, Melissa A.
AU - Kulkarni-Narla, Anjali
AU - Vulchanova, Lucy
AU - Brown, David R.
PY - 2004/12
Y1 - 2004/12
N2 - Enteric neurotransmitters can modulate the biodefensive functions of the intestinal mucosa, but their role in mucosal interactions with enteropathogens is not well defined. Here we tested the hypothesis that norepinephrine (NE) modulates interactions between enterohemorrhagic Escherichia coli O157:H7 (EHEC) and the colonic epithelium. Mucosal sheets from porcine distal colon were mounted in Ussing chambers. Drugs and an inoculum of either Shiga toxin-negative or -positive EHEC were added to the contraluminal and luminal bathing medium, respectively. After 90 min, adherent bacteria were quantified by an adherence assay and by immunohistochemical methods; short-circuit current (Isc) was measured continuously to assess changes in active ion transport. NE-treated tissues exhibited concentration-dependent increases in Isc and EHEC adherence. NE did not alter adherence of a rodent-adapted, noninfectious E. coli strain or two porcine-adapted non-O157 E. coli strains. The actions of NE on EHEC adherence but not Isc were prevented by the α-adrenergic antagonist yohimbine and the PKA activator Sp-8-bromoadenosine-3′, 5′-cyclic monophosphorothioate. Like NE, the PKA inhibitor Rp-8-bromoadenosine-3′,5′-cyclic monophosphorothioate or indirectly acting sympathomimetic agents increased EHEC adherence. Nerve fibers immunoreactive for the NE-synthesizing enzymes tyrosine hydroxylase and dopamine β-hydroxylase appeared to innervate the colonic epithelium. EHEC-like immunoreactivity on the colonic surface had the appearance of bacterial microcolonies and increased after NE treatment by a phentolamine-sensitive mechanism. Through interactions with α2-adrenergic receptors, NE appears to increase EHEC adherence to the colonic mucosa. Changes in sympathetic neural outflow may alter intestinal susceptibility to infection.
AB - Enteric neurotransmitters can modulate the biodefensive functions of the intestinal mucosa, but their role in mucosal interactions with enteropathogens is not well defined. Here we tested the hypothesis that norepinephrine (NE) modulates interactions between enterohemorrhagic Escherichia coli O157:H7 (EHEC) and the colonic epithelium. Mucosal sheets from porcine distal colon were mounted in Ussing chambers. Drugs and an inoculum of either Shiga toxin-negative or -positive EHEC were added to the contraluminal and luminal bathing medium, respectively. After 90 min, adherent bacteria were quantified by an adherence assay and by immunohistochemical methods; short-circuit current (Isc) was measured continuously to assess changes in active ion transport. NE-treated tissues exhibited concentration-dependent increases in Isc and EHEC adherence. NE did not alter adherence of a rodent-adapted, noninfectious E. coli strain or two porcine-adapted non-O157 E. coli strains. The actions of NE on EHEC adherence but not Isc were prevented by the α-adrenergic antagonist yohimbine and the PKA activator Sp-8-bromoadenosine-3′, 5′-cyclic monophosphorothioate. Like NE, the PKA inhibitor Rp-8-bromoadenosine-3′,5′-cyclic monophosphorothioate or indirectly acting sympathomimetic agents increased EHEC adherence. Nerve fibers immunoreactive for the NE-synthesizing enzymes tyrosine hydroxylase and dopamine β-hydroxylase appeared to innervate the colonic epithelium. EHEC-like immunoreactivity on the colonic surface had the appearance of bacterial microcolonies and increased after NE treatment by a phentolamine-sensitive mechanism. Through interactions with α2-adrenergic receptors, NE appears to increase EHEC adherence to the colonic mucosa. Changes in sympathetic neural outflow may alter intestinal susceptibility to infection.
KW - Colonocyte
KW - Enteritis
KW - Protein kinase A
KW - Sympathetic nervous system
KW - α-adrenergic receptor
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UR - http://www.scopus.com/inward/citedby.url?scp=9244223115&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.00471.2003
DO - 10.1152/ajpgi.00471.2003
M3 - Article
C2 - 15534374
AN - SCOPUS:9244223115
SN - 0193-1857
VL - 287
SP - G1238-G1246
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 6 50-6
ER -