Expression of the adhesion molecules ICAM-1, VCAM-1, LFA-1 and VLA-4 in the skin is modulated in progressing stages of chronic venous insufficiency

In inflammation and wound healing, dynamic changes in cell adhesion and mig ration are fundamental properties of the cells involved. Disturbed interact ion of leukocytes with microvascular endothelial cells has been proposed to be a central pathogenic factor in chronic venous insufficiency, This disea se may therefore serve to elucidate dysregulated modulation of adhesion mol ecule expression in conditions of chronic inflammation and impaired wound h ealing. In this study, we determined how the expression of ICAM-1/VCAM-1 on endothelial cells and their ligands LFA-1/VLA-4 on leukocytes is modulated in skin of progressing stages of chronic venous insufficiency. Immunohisto chemical staining of skin biopsies revealed an increase in the expression o f ICAM-1 and VCAM-1 on endothelial cells in an early stage of venous diseas e such as stasis dermatitis. Such protein expression correlated with an inc rease of corresponding mRNA in skin biopsies. Expression of these CAMs on e ndothelial cells was accompanied by the occurrence of a marked perivascular infiltration of leukocytes, which expressed increased levels of LFA-1 and VLA-4, In progressing stages of chronic venous insufficiency, characterized by hyperpigmentation and lipodermatosclerosis, which precede skin ulcerati on, all these CAMs remained upregulated on endothelial cells and infiltrati ng leukocytes, Our findings indicate that following an initial peak express ion during stasis dermatitis, vascular ICAM-1 and VCAM-1 expression is not downmodulated to baseline levels, but remains upregulated, This possibly pr omotes tissue damage by a perpetuated, upregulated influx of activated leuk ocytes, finally leading to skin ulceration.