title: VCAM-1 blockade delays disease onset, reduces disease severity and inflammatory cells in an atopic dermatitis model.
abstract: We investigated the functions of critical adhesion molecules ICAM-1 and VCAM-1 in a keratin-14 IL-4-transgenic (Tg) mouse model of atopic dermatitis, the skin lesions of which are characterized by prominent inflammatory cell infiltration, significantly increased mRNAs and proteins of ICAM-1, VCAM-1, E-selectin, P-selectin, L-selectin, and PSGL-1, and significantly increased numbers of dermal vessels expressing these adhesion molecules. We tested the hypotheses that deletion or blockade of these molecules may impede the inflammation by examining the disease progresses in the Tg mice crossed with ICAM-1-knockout mice and Tg mice received anti-VCAM-1-neutralizing antibody. Although the findings of the ICAM-1-knockout Tg mice (Tg/ICAM-1(-/-)) developed skin lesions similar to wide-type ICAM-1 Tg mice (Tg/ICAM-1(+/+)) were surprising, a compensatory mechanism may account for it: the frequency of VCAM-1 ligand, CD49d, on CD3(+) T cells in the lesional skin significantly increased in the Tg/ICAM-1(-/-) mouse, compared with the Tg/ICAM-1(+/+) mice. In contrast, anti-VCAM-1-treated Tg/ICAM-1(-/-) or Tg/ICAM-1(+/+) mice had significantly delayed onset of skin inflammation compared with isotype antibody-treated groups. Moreover, anti-VCAM-1 significantly reduced the skin inflammation severity in Tg/ICAM-1(+/+) mice, accompanied with reduction of mast cell, eosinophil, and CD3(+) T cell infiltration. VCAM-1 is more critical in developing skin inflammation in this model.
authors.affiliation: Department of Dermatology, University of Illinois, Chicago, IL 60612, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Shao-xia
authors.initials: SX
authors.lastname: Lin
authors.forename: Sanober
authors.initials: S
authors.lastname: Amin
authors.forename: Lut
authors.initials: L
authors.lastname: Overbergh
authors.forename: Giacomo
authors.initials: G
authors.lastname: Maggiolino
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Chan
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology*; D002465:Cell Movement / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053547:Keratin-14 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019041:L-Selectin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019007:P-Selectin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D019040:E-Selectin; D053547:Keratin-14; C507446:Krt14 protein, mouse; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D019007:P-Selectin; C084882:P-selectin ligand protein; D019010:Vascular Cell Adhesion Molecule-1; D019041:L-Selectin