Adhesion molecules in atopic dermatitis: VCAM-1 and ICAM-1 expression is increased in healthy-appearing skin

Abstract

In the skin of normal and atopic individuals, the expression of E‐selecting (ELAM‐l), L‐selectin (LECAM‐l), P‐selection (CD62), CD31 (PECAM), vascular cell adhesion molecule‐1 (VCAM‐l), intercellular adhesion molecule‐1 (ICAM‐l), and cutaneous lymphocyte antigen (CLA) were compared by immunostaining of skin biopsies which were taken from normal individuals (n= 17), the healthy‐appearing skin of patients with atopic dermatitis (n = lo), and their acute (n = 5) and chronic (n = 6) skin lesions. In contrast to ELAM‐1, the expression of VCAM‐1 and ICAM‐1 was found to be significantly increased in non lesional atopic skin in comparison to the skin of normal individuals. Moreover, in contrast to normal skin of healthy individuals, nonlesional atopic skin showed a further increase of VCAM‐1, ICAM‐1, and ELAM‐1 when cultured with medium alone. This suggests that certain adhesion molecules are constitutively upregulated in healthy‐appearing skin of patients with atopic dermatitis. In addition, atopic skin appears to respond to nonspecific stimuli (such as culture with medium alone) with upregulation of VCAM‐1, ICAM‐1, and ELAM‐1. It is suggested that the observed upregulation of adhesion molecules is mediated by the release of cytokines such as interleukin‐4 from cells which reside in atopic skin. The question of whether the inherent up regulation of adhesion molecules in atopic skin contributes to the development of Th2 cells, which have been found to predominate in atopic inflammation, has to be further investigated.

Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice.

“…In the chronic skin lesions of AD, cells containing IFN-␥ mRNA and protein predominate over those containing IL-4 and IL-5 (3). Vascular endothelial cells in AD skin lesions have increased expression of the adhesion molecules E-selectin, VCAM-1, and ICAM-1 (4,5). Products of eosinophils, which express VLA-4, the counterligand for VCAM-1, are readily detectable in the skin lesions of AD (6).…”

Adhesion molecule profiles in atopic dermatitis vs. allergic contact dermatitis: pharmacological modulation by cetirizine

“…This is unsurprising as this phenomenon, which was already described, results from a selective activation of Th2 cells producing the cocktail of cytokines known to induce this selective overexpression of adhesion molecules 11–13 and more especially IL‐4 and TNF‐α. This release of cytokines can happen in situ in the skin as it was shown that skin cultures without exogenous cytokines showed upregulated adhesion molecules expression in healthy‐appearing skin of AD subjects 14 . In the case of ACD patients, the expression of ICAM‐1 is already highly expressed in normal skin, as already observed by others, 4,15 and this expression is not significantly modified after challenge.…”

VCAM‐1 blockade delays disease onset, reduces disease severity and inflammatory cells in an atopic dermatitis model

“…In human beings with AD, the endothelial expressions of ICAM‐1 and VCAM‐1 were found to be significantly increased in the healthy‐appearing skin (non‐lesional skin) of these patients compared with the skin of normal individuals 12 . The non‐lesional skin showed a further increase of ICAM‐1 and VCAM‐1 expressions when cultured with medium alone, suggesting that these adhesion molecules are constitutively upregulated in the non‐lesional skin of AD possibly because of the cytokines such as IL‐4 released by cells in the skin 12 . When the skin lesions developed, the endothelial expressions of ICAM‐1 and VCAM‐1 were found markedly increased in the lesional skin of AD patients compared with normal individuals 13 , 14 , 15 .…”