Nitric Oxide Participates in the Recovery of Normal Jejunal Epithelial Ion Transport Following Exposure to the Superantigen, Staphylococcus aureus Enterotoxin B

• Published in: The Journal of immunology (1950) 1999-10, Vol.163 (8), p.4519-4526
• Main Authors: McKay, Derek M, Lu, Jun, Jedrzkiewicz, Sean, Ho, Winnie, Sharkey, Keith A
• Format: Article
• Language: English
• Subjects: Animals; Enterotoxins - pharmacology; Enzyme Inhibitors - pharmacology; Epithelial Cells - enzymology; Epithelial Cells - immunology; Epithelial Cells - metabolism; Immune Sera - pharmacology; Interferon-gamma - immunology; Interferon-gamma - metabolism; Ion Transport - immunology; Jejunum - enzymology; Jejunum - immunology; Jejunum - metabolism; Lysine - analogs & derivatives; Lysine - pharmacology; Male; Mice; Mice, Inbred BALB C; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type II; Penicillamine - analogs & derivatives; Penicillamine - pharmacology; Staphylococcus aureus; Staphylococcus aureus - immunology; Superantigens - pharmacology; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.163.8.4519

Bacterial superantigens (SAgs) are potent T cell activators. Mice treated 4 h previously with the SAg, Staphylococcus aureus enterotoxin B (SEB), display reduced ion transport (assessed by short circuit current) responses to prosecretory stimuli, which normalize 24 h posttreatment. Here, mice were treated with SEB alone or in combination with an inhibitor of the inducible form of NO synthase (iNOS), l -NIL. Subsequently, jejunal iNOS expression was detected by immunohistochemistry, ion transport was evaluated in Ussing chambers, and serum levels of TNF-alpha and IFN-gamma were measured by ELISA. SEB-treated mice had increased epithelial iNOS immunoreactivity, and numerous iNOS-positive CD3+ T cells occurred in their mucosa and submucosa. Concomitant treatment with l -NIL did not affect the reduced short circuit current responsiveness to electrical nerve stimulation or the prosecretory agents, carbachol and forskolin, that occurred 4 h post-SEB (5 microgram) treatment. However, Isc responses in l -NIL- plus SEB-treated mice were still significantly reduced 24 h posttreatment, indicating a role for NO in the restoration of normal ion transport following exposure to SAgs. The prolongation of epithelial ion transport abnormalities correlated with elevated serum levels of TNF-alpha and IFN-gamma in mice treated 24 h previously with l -NIL plus SEB compared with those in controls and SEB-only-treated mice. Additionally, mice treated with l -NIL plus SEB and TNF-alpha- or IFN-gamma-neutralizing Abs displayed normal jejunal ion transport characteristics 24 h posttreatment. We conclude that NO mobilization is important in the homeostatic recovery response following immune stimulation by SAgs and that the beneficial effect of NO in this model system is probably via regulation of TNF-alpha and IFN-gamma production.