title: Differential expression of TRAIL and TRAIL receptors in allergic asthmatics following segmental antigen challenge: evidence for a role of TRAIL in eosinophil survival.
abstract: Asthma is a chronic lung disease exhibiting airway obstruction, hyperresponsiveness, and inflammation, characterized by the infiltration of eosinophils into the airways and the underlying tissue. Prolonged eosinophilic inflammation depends on the balance between the cell's inherent tendency to undergo apoptosis and the local eosinophil-viability enhancing activity. TRAIL, a member of the TNF family, induces apoptosis in most transformed cells; however, its role in health and disease remains unknown. To test the hypothesis that Ag-induced inflammation is associated with TRAIL/TRAIL-R interactions, we used a segmental Ag challenge (SAC) model in ragweed-allergic asthmatics and nonasthmatic patients and analyzed bronchoalveolar lavage (BAL) material for 2 wk. In asthmatic patients, the level of TRAIL in BAL fluid dramatically increased 24 h after SAC, which significantly correlated with BAL eosinophil counts. Immunohistochemical analysis of bronchial biopsies from asthmatic patients demonstrated that TRAIL staining was increased in epithelial, airway smooth muscle, and vascular smooth muscle cells and throughout the interstitial tissue after SAC. This was confirmed by quantitative immunocytochemical image analysis of BAL eosinophils and alveolar macrophages, which demonstrated that expression levels of TRAIL and DcR2 increased, whereas expression levels of the TRAIL-Rs DR4 and DR5 decreased in asthmatic subjects after SAC. We also determined that TRAIL prolongs eosinophil survival ex vivo. These data provide the first in vivo evidence that TRAIL expression is increased in asthmatics following Ag provocation and suggest that modulation of TRAIL and TRAIL-R interactions may play a crucial role in promoting eosinophil survival in asthma.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, Bluemle Life Science Building, Suite 331, Thomas Jefferson University, Philadelphia, PA 19107, USA. Noreen.Robertson@mail.tju.edu
authors.forename: Noreen M
authors.initials: NM
authors.lastname: Robertson
authors.forename: James G
authors.initials: JG
authors.lastname: Zangrilli
authors.forename: Andrzej
authors.initials: A
authors.lastname: Steplewski
authors.forename: Annette
authors.initials: A
authors.lastname: Hastie
authors.forename: Rochelle G
authors.initials: RG
authors.lastname: Lindemeyer
authors.forename: Maria A
authors.initials: MA
authors.lastname: Planeta
authors.forename: Mary K
authors.initials: MK
authors.lastname: Smith
authors.forename: Nathalie
authors.initials: N
authors.lastname: Innocent
authors.forename: Ali
authors.initials: A
authors.lastname: Musani
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Pascual
authors.forename: Stephen
authors.initials: S
authors.lastname: Peters
authors.forename: Gerald
authors.initials: G
authors.lastname: Litwack
mesh_terms: D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D001999:Bronchoscopy; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology / Q000502:physiology*; D008565:Membrane Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000096:biosynthesis*; D012995:Solubility; D053221:TNF-Related Apoptosis-Inducing Ligand; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology*
chemical_list: D000485:Allergens; D051017:Apoptosis Regulatory Proteins; D007106:Immune Sera; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C451501:TNFRSF10D protein, human; C505653:TNFSF10 protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha