Drug-induced expression of intercellular adhesion molecule-1 on lesional keratinocytes in fixed drug eruption.
The mechanism(s) and the factor(s) that contribute to preferential localization of fixed drug eruption (FDE) lesions to certain skin sites remain speculative. Previous studies suggested that populations of T cells residing in the lesional epidermis may be involved in selective destruction of the epidermis in FDE. In this study, to define the earliest cellular and molecular events with potential relevance to activation of the epidermal T cells, expression of adhesion molecules on keratinocytes (KC) and vascular endothelium was examined sequentially in the lesional skin of FDE patients after challenge with the causative drug. Rapid and intense intercellular adhesion molecule-1 (ICAM-1) expression was induced on the vascular endothelium and KC as early as 1.5 hours after challenge, at which time E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were not up-regulated. In vitro studies using skin organ culture showed that the lesional KC and endothelium responded more rapidly and intensely to express ICAM-1 to tumor necrosis factor-alpha or interferon-gamma compared with those in the nonlesional skin. Surprisingly, such selective induction of KC ICAM-1 restricted to the lesional skin was also observed after exposure to the causative drug alone in skin organ culture. Pretreatment of the lesional skin with anti-tumor necrosis factor completely abrogated in vitro induction of KC ICAM-1 expression by the drug. Drug-induced, TNF-alpha-dependent KC ICAM-1 expression in the lesional skin suggests that induction of ICAM-1 expression by the lesional KC after ingestion of the drug would probably provide a localized initiating stimulus for activation of the disease-associated epidermal T cells.
Teraki
Y
Y
Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
Moriya
N
N
Shiohara
T
T
D000293:Adolescent; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003875:Drug Eruptions / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D015603:Keratinocytes / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D009924:Organ Culture Techniques; D011398:Promethazine / Q000008:administration & dosage; D012457:Salicylamides / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000473:pathology; D013997:Time Factors
D015815:Cell Adhesion Molecules; D012457:Salicylamides; D018799:Intercellular Adhesion Molecule-1; D011398:Promethazine; C018935:ethenzamide