Suppression of the murine gut mucosal IgA response to cholera toxin with oral cyclosporine.
The gut mucosal immune system may be a primary target for many ingested chemicals. Methods have been developed to examine the effects of chemicals on the systemic humoral immune response; however, studies to evaluate various methods of assessing the local gut mucosal immune response in a toxicology assay have been limited. The objectives of this study were to examine the effects of the known immunosuppressive compound, cyclosporine (CYS), on the generation of a cholera toxin (CT)-specific gut mucosal IgA response and evaluate the methods used to measure the gut IgA response. Groups of female B6C3F1 mice were left untreated or were treated daily, p.o., with corn oil (vehicle) or CYS at doses of 10 and 50 mg/kg for 20 days. On Days 3 and 13, mice were sensitized p.o. with CT. On Day 21, mice were terminated, gut washings were collected, and lamina propria lymphocytes were extracted from gut tissue with collagenase treatment. Cholera toxin-specific IgA in the gut washings was measured by an ELISA. The numbers of CT-specific IgA (CT-IgA) and total IgA antibody-forming cells (spot-forming cells, SFC) obtained from the lamina propria were determined by the ELISPOT method. A dose of 50 mg/kg CYS produced a significant decrease in the amount of CT-IgA in gut washings. This dose also decreased the number of cells recovered from the lamina propria by at least 50%. The amount of CT-specific SFC/million lamina propria cells decreased with a dose of 10 mg/kg CYS, whereas 50 mg/kg CYS did not alter the response.(ABSTRACT TRUNCATED AT 250 WORDS)
Kawabata
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Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond 23298.
Lin
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Ladics
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D000284:Administration, Oral; D000818:Animals; D002772:Cholera Toxin / Q000276:immunology*; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains
D007071:Immunoglobulin A, Secretory; D016572:Cyclosporine; D002772:Cholera Toxin