Apoptosis underlies immunopathogenic mechanisms in acute silicosis.
We investigated immunopathogenic roles for apoptosis in acute murine silicosis. Intratracheal silica instillation induced pulmonary inflammation and enlarged thoracic lymph nodes. Lymphocytes from silica-exposed lymph nodes showed reduced mitogenic responses to T cell receptor (TCR) stimulation, and markedly increased activation-induced cell death, compared with control lymphocytes from saline-exposed lymph nodes. CD4(+) T cell death was mediated by Fas ligand, because CD4(+) T cells from Fas ligand-deficient gld mice did not undergo activation-induced apoptosis. Silica deposition also resulted in increased apoptosis associated with inflammatory infiltrates in lung parenchyma. In vivo treatment with caspase inhibitors reduced neutrophil accumulation, and alleviated inflammation in the lungs of silica-treated mice. These results suggest that silica-induced apoptosis plays an inflammatory role in the lung parenchyma, and creates immunologic abnormalities in regional lymph nodes, with pathogenic implications for the host.
Borges
Valeria M
VM
Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, Brazil.
Lopes
Marcela F
MF
Falcão
Haroldo
H
Leite-Júnior
José Henrique
JH
Rocco
Patricia R M
PR
Davidson
Wendy F
WF
Linden
Rafael
R
Zin
Walter A
WA
DosReis
George A
GA
D000208:Acute Disease; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000276:immunology* / Q000502:physiology; D061945:Caspase Inhibitors; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects; D012822:Silicon Dioxide / Q000009:adverse effects*; D012829:Silicosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D013909:Thorax / Q000276:immunology / Q000502:physiology
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012822:Silicon Dioxide