Adrenergic modulation of Escherichia coli O157:H7 adherence to the colonic mucosa.
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 (I(sc)) was measured continuously to assess changes in active ion transport. NE-treated tissues exhibited concentration-dependent increases in I(sc) 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 I(sc) were prevented by the alpha-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 beta-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 alpha(2)-adrenergic receptors, NE appears to increase EHEC adherence to the colonic mucosa. Changes in sympathetic neural outflow may alter intestinal susceptibility to infection.
Green
Benedict T
BT
Pharmacology Section, Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Ave., St. Paul, Minnesota 55108-6010, USA.
Lyte
Mark
M
Chen
Chunsheng
C
Xie
Yonghong
Y
Casey
Melissa A
MA
Kulkarni-Narla
Anjali
A
Vulchanova
Lucy
L
Brown
David R
DR
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D001693:Biological Transport, Active / Q000502:physiology; D003106:Colon / Q000294:innervation* / Q000382:microbiology*; D004594:Electrophysiology; D019453:Escherichia coli O157 / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000294:innervation* / Q000382:microbiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology; D013552:Swine; D013564:Sympathetic Nervous System / Q000502:physiology*
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D018759:Adrenergic Uptake Inhibitors; D007473:Ion Channels; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009638:Norepinephrine