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 -