Epidermal calprotectin in drug-induced toxic epidermal necrolysis.
Calcium ions (Ca++) in excess alter cell viability. Their potential role in drug-induced toxic epidermal necrolysis (TEN) was investigated. Thirteen TEN patients were biopsied at the site of early bullous lesions and on clinically normal-looking skin at least 2 cm distant from blisters. Immunohistochemistry was applied using the mouse monoclonal antibody Mac 387 recognizing the cytosolic protein complex L1 (calprotectin). The L1 antigen is a calcium-binding protein expressed by human granulocytes, monocytes-macrophages and injured epidermis, but not by normal epidermis and other cells harboured in the skin. The majority (8/13) of TEN samples from apparently non-involved skin expressed the L1 antigen in a patch-like pattern inside the epidermis where inflammatory cells were scant or absent. As assessed by computerized image analysis of TEN bullous skin, the intensity of the L1 expression in the epidermis was not statistically correlated with the amount of the infiltrating inflammatory cells (Mac 387+ macrophages, UCLH1 + T lymphocytes and Factor XIIIa+ dendrocytes) present in the dermis and in the epidermis. Such findings suggest a key role for keratinocytes in the production of the L1 calcium-binding complex. As the L1 complex formation is a calcium-dependent process, one of the first biological events in TEN could be a dramatic increase in keratinocytes intracellular Ca++ concentration following damage by the involved drug metabolites. The ultimate toxic cell dysregulation would result from the disturbance in the intracellular Ca++ homeostasis.
Paquet
P
P
Department of Dermatopathology, University of Liège, CHU Sart Tilman, Belgium.
Piérard
G E
GE
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002452:Cell Count; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D039841:Leukocyte L1 Antigen Complex; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules