title: Fas ligand triggers pulmonary silicosis.
abstract: We investigated the role of Fas ligand in murine silicosis. Wild-type mice instilled with silica developed severe pulmonary inflammation, with local production of tumor necrosis factor (TNF)-alpha, and interstitial neutrophil and macrophage infiltration in the lungs. Strikingly, Fas ligand-deficient generalized lymphoproliferative disease mutant (gld) mice did not develop silicosis. The gld mice had markedly reduced neutrophil extravasation into bronchoalveolar space, and did not show increased TNF-alpha production, nor pulmonary inflammation. Bone marrow chimeras and local adoptive transfer demonstrated that wild-type, but not Fas ligand-deficient lung macrophages recruit neutrophils and initiate silicosis. Silica induced Fas ligand expression in lung macrophages in vitro and in vivo, and promoted Fas ligand-dependent macrophage apoptosis. Administration of neutralizing anti-Fas ligand antibody in vivo blocked induction of silicosis. Thus, Fas ligand plays a central role in induction of pulmonary silicosis.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21944-970, Rio de Janeiro, Brazil.
authors.forename: V M
authors.initials: VM
authors.lastname: Borges
authors.forename: H
authors.initials: H
authors.lastname: Falcão
authors.forename: J H
authors.initials: JH
authors.lastname: Leite-Júnior
authors.forename: L
authors.initials: L
authors.lastname: Alvim
authors.forename: G P
authors.initials: GP
authors.lastname: Teixeira
authors.forename: M
authors.initials: M
authors.lastname: Russo
authors.forename: A F
authors.initials: AF
authors.lastname: Nóbrega
authors.forename: M F
authors.initials: MF
authors.lastname: Lopes
authors.forename: P M
authors.initials: PM
authors.lastname: Rocco
authors.forename: W F
authors.initials: WF
authors.lastname: Davidson
authors.forename: R
authors.initials: R
authors.lastname: Linden
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: W A
authors.initials: WA
authors.lastname: Zin
authors.forename: G A
authors.initials: GA
authors.lastname: DosReis
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D005260:Female; D066298:In Vitro Techniques; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000473:pathology; D011828:Radiation Chimera; D012822:Silicon Dioxide / Q000633:toxicity; D012829:Silicosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D012822:Silicon Dioxide