TY - JOUR

T1 - Immunohistochemical detection of the apoptosis-related proteins FADD, FLICE, and FLIP in Langerhans cell histiocytosis

AU - Bank, Micha I

AU - Gudbrand, Charlotte

AU - Lundegaard, Pia Rengtved

AU - Carstensen, Henrik

AU - Fadeel, Bengt

AU - Henter, Jan-Inge

AU - Petersen, Bodil Laub

PY - 2005/6

Y1 - 2005/6

N2 - Langerhans cell histiocytosis (LCH) is characterized by an accumulation of dendritic Langerhans cells in granulomatous lesions in various organs. The etiology of LCH remains enigmatic. Fas/APO-1/CD95 belongs to the "death receptor" family of apoptosis regulators and has been implicated in the downregulation of immune responses. The authors examined the expression of three proteins that are engaged in the Fas signaling cascade-FADD/Fas-associated death domain-containing protein, FLICE/FADD-like interleukin-1beta-converting enzyme (both pro-apoptotic), and FLIP/FLICE-inhibitory protein (anti-apoptotic)-in lesions from LCH patients. Immunohistochemistry was performed on paraffin-embedded tissue specimens from 43 children with LCH. The infiltrates were scored according to the amount of positive pathologic Langerhans cells (pLCs). In all investigated specimens, the majority of the pLCs expressed FADD, active FLICE, and FLIP. The clinical outcome of the disease could not be correlated to the expression of the investigated proteins. This study shows a high expression of the apoptosis-related proteins FADD, active FLICE, and FLIP in pLCs. The authors previously showed that pLCs express Fas and Fas ligand. Taken together, these findings suggest that the Fas signaling pathway may be involved in the pathogenesis of LCH.

AB - Langerhans cell histiocytosis (LCH) is characterized by an accumulation of dendritic Langerhans cells in granulomatous lesions in various organs. The etiology of LCH remains enigmatic. Fas/APO-1/CD95 belongs to the "death receptor" family of apoptosis regulators and has been implicated in the downregulation of immune responses. The authors examined the expression of three proteins that are engaged in the Fas signaling cascade-FADD/Fas-associated death domain-containing protein, FLICE/FADD-like interleukin-1beta-converting enzyme (both pro-apoptotic), and FLIP/FLICE-inhibitory protein (anti-apoptotic)-in lesions from LCH patients. Immunohistochemistry was performed on paraffin-embedded tissue specimens from 43 children with LCH. The infiltrates were scored according to the amount of positive pathologic Langerhans cells (pLCs). In all investigated specimens, the majority of the pLCs expressed FADD, active FLICE, and FLIP. The clinical outcome of the disease could not be correlated to the expression of the investigated proteins. This study shows a high expression of the apoptosis-related proteins FADD, active FLICE, and FLIP in pLCs. The authors previously showed that pLCs express Fas and Fas ligand. Taken together, these findings suggest that the Fas signaling pathway may be involved in the pathogenesis of LCH.

KW - Adaptor Proteins, Signal Transducing

KW - Apoptosis

KW - CASP8 and FADD-Like Apoptosis Regulating Protein

KW - Caspase 8

KW - Caspases

KW - Child

KW - Enzyme Activation

KW - Fas-Associated Death Domain Protein

KW - Histiocytosis, Langerhans-Cell

KW - Humans

KW - Immunohistochemistry

KW - Intracellular Signaling Peptides and Proteins

KW - Palatine Tonsil

M3 - Journal article

C2 - 15956881

VL - 27

SP - 301

EP - 306

JO - Journal of Pediatric Hematology/Oncology

JF - Journal of Pediatric Hematology/Oncology

SN - 1077-4114

IS - 6

ER -