title: Immunohistochemical detection of the apoptosis-related proteins FADD, FLICE, and FLIP in Langerhans cell histiocytosis.
abstract: 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.
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Micha I
authors.initials: MI
authors.lastname: Bank
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gudbrand
authors.forename: Pia
authors.initials: P
authors.lastname: Rengtved
authors.forename: Henrik
authors.initials: H
authors.lastname: Carstensen
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.forename: Bodil Laub
authors.initials: BL
authors.lastname: Petersen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D002648:Child; D004789:Enzyme Activation; D053200:Fas-Associated Death Domain Protein; D006646:Histiocytosis, Langerhans-Cell / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D014066:Palatine Tonsil / Q000166:cytology / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D047908:Intracellular Signaling Peptides and Proteins; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases