title: Associations between IL-13 and IL-4 (mRNA and protein), vascular cell adhesion molecule-1 expression, and the infiltration of eosinophils, macrophages, and T cells in allergen-induced late-phase cutaneous reactions in atopic subjects.
abstract: IL-13, like IL-4, induces up-regulation of vascular cell adhesion molecule-1 (VCAM-1) expression on human endothelial cells in vitro. This may contribute to local accumulation of alpha4beta1+ inflammatory cells, such as eosinophils, macrophages, and T cells. We tested the hypothesis that in human allergic inflammatory reactions in vivo, IL-13 and IL-4 are both involved in VCAM-1/alpha4beta1-dependent recruitment of inflammatory cells. Cryostat cutaneous sections from 13 atopic subjects taken 6, 24, and 48 h after allergen challenge were processed for immunohistochemical staining and in situ hybridization using mAbs and 35S-labeled riboprobes for IL-4 and IL-13. When compared with diluent sites, allergen provoked significant increases in the numbers of cells that were mRNA+ and protein-positive for both IL-13 and IL-4 that were clearly demonstrable at 6 h, peaked at 24 h, and declined by 48 h. Double immunohistochemical staining/in situ hybridization showed that the majority (>60%) of IL-13 mRNA+ signals were colocalized to CD3+ T cells. The numbers of mRNA+ and protein-positive cells for IL-13 significantly correlated with VCAM-1 immunoreactivity on endothelial cells and with total numbers of infiltrating EG2+ eosinophils, CD45RO+ T cells, and CD68+ macrophages, but not elastase-positive neutrophils, at the 6- and 24-h time points. At 6 h, an association was also observed between the numbers of IL-4 mRNA+ or protein product-positive cells and VCAM-1 expression, although this was not statistically significant. These findings suggest that IL-13 may play an important role in recruitment of inflammatory cells to the site of cutaneous allergic inflammatory reaction through VCAM-1/alpha4beta1-dependent mechanisms.
authors.affiliation: Allergy and Clinical Immunology, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Ying
authors.forename: Q
authors.initials: Q
authors.lastname: Meng
authors.forename: L T
authors.initials: LT
authors.lastname: Barata
authors.forename: D S
authors.initials: DS
authors.lastname: Robinson
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: A B
authors.initials: AB
authors.lastname: Kay
mesh_terms: D000328:Adult; D000485:Allergens; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007158:Immunologic Techniques; D017403:In Situ Hybridization; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D000485:Allergens; D018793:Interleukin-13; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4