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Página de Inicio arrow Artículos Científicos arrow VCAM-1 blockade delays disease onset, reduces disease severity and inflammatory cells in an atopic dermatitis model
VCAM-1 blockade delays disease onset, reduces disease severity and inflammatory cells in an atopic dermatitis model Imprimir E-Mail
VCAM-1 blockade delays disease onset, reduces disease severity and inflammatory cells in an atopic dermatitis model
Lin Chen1, Shao-xia Lin1, Sanober Amin1, Lut Overbergh2, Giacomo Maggiolino1 and Lawrence S Chan1,3,4
Immunology and Cell Biology advance online publication 12 January 2010;

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.
 
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