E‐selectin and vascular cell adhesion molecule‐1 as critical adhesion molecules for infiltration of T lymphocytes and eosinophils in atopic dermatitis

Abstract

To study the temporal and spatial relationship between infiltrating T-cell subsets or eosinophils and cell adhesion molecules on endothelial cells in skin lesions of atopic dermatitis (AD), we undertook immunohistochemical analysis using monoclonal antibodies against surface markers of T cells, eosinophil granule proteins and cell adhesion molecules. Predominant mononuclear cells in acute and chronic skin lesions were CD3, CD4 and CD45RO positive helper-inducer/memory T cells. Their number was significantly and strongly correlated with the intensity of E-selectin expression. Eosinophils and deposition of eosinophil-derived granule proteins such as eosinophil cationic protein (ECP), major basic protein (MBP) and eosinophil peroxidase (EPO) were found constantly in acute lesions and only occasionally in chronic lesions. The total number of immunoreactive eosinophils and deposits of MBP, EPO and ECP were significantly and strongly correlated with the staining intensity of VCAM-1. In chronic lesions significant reduction of VCAM-1 expression paralleled occasional infiltration of eosinophils. Our results demonstrate the possibility that E-selectin and VCAM-1 are the critical adhesion molecules for trafficking of memory T cells and eosinophils, respectively, into skin lesion of AD. Persistent expression of the adhesion molecules may be related to prolongation of the skin lesion in AD.

Assessment of Epidermal Barrier Function by Photoacoustic Spectrometry in Relation to Its Importance in the Pathogenesis of Atopic Dermatitis

“…The patients did not apply any ointment or cream on the examined sites for at least 5 days before the measurements. Concerning the inflammatory state at the clinically normal tested sites, we have previously demonstrated that clinically normal skin from patients with AD has no histologic evidence of inflammation (Wakita et al, 1994), suggesting that in the current study, no substantial inflammatory changes were present in the nonlesional skin.…”

“…Since clinically normal skin in patients with AD has minimal or no inflammation (Wakita et al, 1994), this observation strongly suggests that defects in the permeability barrier function in AD are intrinsic and are not associated with inflammatory events. Although there was a significant increase both in PA signals and in TEWL values in AD compared with healthy controls, the degree of barrier disruption in AD expressed as a relative ratio to healthy controls was greater with the PAS method (2.98-to 1.8-fold) than with the TEWL measurement (1.73-fold).…”

Recharacterization of the Nonlesional Dry Skin in Atopic Dermatitis through Disrupted Barrier Function

“…Collectively, our fi ndings suggest that cutaneous infl ammatory reaction induced by a variety of environmental irritants and allergens or scratching may trigger the expression of susceptibility gene, probably including sphingomyeline/glucosylceramide deacylase enzyme, resulting in the ceramide defi ciency which in turn leads to the barrier disruption in the AD skin. It seems reasonable to assume that once-expressed susceptibility gene never disappears for a long period of time, even after infl ammation is attenuated, in turn leading to the continued barrier disruption even in the nonlesional skin without any infl ammation [30] .…”

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).…”