title: Mucosal vaccination increases endothelial expression of mucosal addressin cell adhesion molecule 1 in the human gastrointestinal tract.
abstract: Homing of leukocytes to various tissues is dependent on the interaction between homing receptors on leukocytes and their ligands, addressins, on endothelial cells. Mucosal immunization results in homing of antigen-specific lymphocytes back to the mucosa where they first encountered the antigen. However, it is unknown whether this homing of antigen-specific cells is mediated by an altered endothelial addressin expression after vaccination. Using different immunization routes with an oral cholera vaccine, we show that the endothelial expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is increased in the gastric and upper small intestinal mucosae after immunization through various local routes in the upper gastrointestinal tract. In contrast, rectal immunization did not influence the levels of MAdCAM-1 in the gastric or duodenal mucosa. Furthermore, we show that MAdCAM-1 can be induced on human endothelial cells by tumor necrosis factor alpha (TNF-alpha) and gamma interferon. The vaccine component cholera toxin B subunit (CTB) increased MAdCAM-1 expression on endothelial cells in cultured human gastric explants, an effect that seemed to be mediated by TNF-alpha. In conclusion, MAdCAM-1 expression is increased in the upper gastrointestinal tract after local immunizations with a vaccine containing CTB. This strongly suggests the involvement of MAdCAM-1 in the preferential homing of mucosal lymphocytes to their original site of activation.
authors.affiliation: Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Center, Göteborg, Sweden. catharina.lindholm@microbio.gu.se
authors.forename: Catharina
authors.initials: C
authors.lastname: Lindholm
authors.forename: Andrew
authors.initials: A
authors.lastname: Naylor
authors.forename: Eva-Liz
authors.initials: EL
authors.lastname: Johansson
authors.forename: Marianne
authors.initials: M
authors.lastname: Quiding-Järbrink
mesh_terms: D000328:Adult; D015815:Cell Adhesion Molecules; D002772:Cholera Toxin / Q000494:pharmacology; D022121:Cholera Vaccines / Q000276:immunology*; D004727:Endothelium / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009088:Mucoproteins / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014611:Vaccination
chemical_list: D015815:Cell Adhesion Molecules; D022121:Cholera Vaccines; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002772:Cholera Toxin