The relationship between allergen-induced tissue eosinophilia and markers of repair and remodeling in human atopic skin.
Several in vitro studies suggest that eosinophils may play a role in fibrosis, remodeling, and repair processes associated with IgE-mediated hypersensitivity. However, the relationship in vivo, between allergen-induced tissue eosinophilia and markers of repair has yet to be established in human atopic subjects. Using the allergen-induced cutaneous late-phase reaction as a model of allergic inflammation, we have tested the hypothesis that eosinophil-derived TGF-beta1 and IL-13 are temporarily associated with myofibroblast formation and deposition of tenascin and procollagen I. Biopsies were taken from atopic volunteers at 1, 3, 6, 24, 48, and 72 h after intradermal allergen challenge and were examined by immunohistochemistry. Following the peak of the late-phase reaction (6 h) there were persisting TGF-beta1(+) eosinophils, alpha-smooth muscle actin(+) myofibroblasts, tenascin immunoreactivity, and procollagen-I(+) cells 24-48 h postchallenge. Direct evidence of generation of repair markers was obtained by coculture of eosinophils and fibroblasts. This resulted in alpha-smooth muscle actin immunoreactivity that was inhibitable by neutralizing Abs to TGF-beta as well as production of tenascin transcripts and protein product. TGF-beta1 and IL-13 also induced tenascin expression. We conclude that TGF-beta1 and IL-13, provided partially by eosinophils, contribute to repair and remodeling events in allergic inflammation in human atopic skin.
Phipps
Simon
S
Department of Allergy and Clinical Immunology, Faculty of Medicine, Imperial College, National Heart and Lung Institute, Dovehouse Street, London, UK, SW3 6LY.
Ying
Sun
S
Wangoo
Arun
A
Ong
Yee-Ean
YE
Levi-Schaffer
Francesca
F
Kay
A Barry
AB
D000199:Actins / Q000037:antagonists & inhibitors; D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007106:Immune Sera / Q000494:pharmacology; D007271:Injections, Intradermal; D018793:Interleukin-13 / Q000096:biosynthesis / Q000494:pharmacology; D007428:Intradermal Tests; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D019063:Tenascin / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000276:immunology; D014945:Wound Healing / Q000276:immunology
D000199:Actins; D000485:Allergens; D015415:Biomarkers; D007106:Immune Sera; D018793:Interleukin-13; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D019063:Tenascin; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2