title: Anti-Fas/CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) differentially regulate apoptosis in normal and neoplastic human basophils.
abstract: Basophilia is associated with allergic and parasitic diseases and advanced chronic myeloid leukemia. In the present study, we characterized the expression and function of the death receptors Fas/CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors in basophils from healthy donors compared to neoplastic basophils. Peripheral blood basophils obtained from healthy donors (HD-PBB) and from patients with chronic myeloid leukemia (CML-PBB) were found to express high levels of Fas/CD95 and low levels of TRAIL-R2, whereas the basophil-like chronic myeloid leukemia cell line KU-812 expressed significant levels of TRAIL-R1 and TRAIL-R2. HD-PBB underwent apoptosis in response to anti-Fas/CD95, but showed resistance to TRAIL, unless they were co-treated with actinomycin D. Interestingly, CML-PBB and KU-812 cells exhibited the opposite response pattern with resistance to anti-Fas/CD95, but significant susceptibility to TRAIL-induced apoptosis. Our data show that anti-Fas/CD95 and TRAIL differentially regulate apoptosis of normal and neoplastic human basophils, which may direct the development of novel therapeutic strategies.
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Förster
authors.forename: Franco H
authors.initials: FH
authors.lastname: Falcone
authors.forename: Bernhard F
authors.initials: BF
authors.lastname: Gibbs
authors.forename: Liane M
authors.initials: LM
authors.lastname: Preussner
authors.forename: Britta S
authors.initials: BS
authors.lastname: Fiebig
authors.forename: Hülya
authors.initials: H
authors.lastname: Altunok
authors.forename: Jens M
authors.initials: JM
authors.lastname: Seeger
authors.forename: Sabine
authors.initials: S
authors.lastname: Cerny-Reiterer
authors.forename: Anja
authors.initials: A
authors.lastname: Rabenhorst
authors.forename: Kerstin
authors.initials: K
authors.lastname: Papenfuss
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Hamid
authors.initials: H
authors.lastname: Kashkar
authors.forename: Karin
authors.initials: K
authors.lastname: Hartmann
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003510:Cyclohexanes; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D019014:fas Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D003510:Cyclohexanes; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D019014:fas Receptor; C000027:cyprodenate