RESUMO
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.
Assuntos
Glicoproteínas de Membrana/fisiologia , Silicose/etiologia , Transferência Adotiva , Animais , Apoptose , Modelos Animais de Doenças , Proteína Ligante Fas , Feminino , Técnicas In Vitro , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Macrófagos/patologia , Masculino , Glicoproteínas de Membrana/deficiência , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Neutrófilos/patologia , Quimera por Radiação , Dióxido de Silício/toxicidade , Silicose/genética , Silicose/patologia , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Long-term survivors (5 or more years) of pneumonectomy for nonsmall cell lung cancer are at risk for late death from cancer recurrence, second primary malignancies, and cardiopulmonary insufficiency related to the adverse physiological effects of pneumonectomy. A retrospective study of pneumonectomy patients was done to quantify the risks of late death from these causes. Of 246 patients treated for nonsmall cell lung cancer by pneumonectomy, medical records of 49 who survived 5 or more years were reviewed. Follow-up for the 49 long-term survivors ranged from 60 to 240 months, with a mean of 113 months. Twenty-five (51%) of the long-term survivors were alive at the time of the study. Twenty-four (49%) had died. Causes of death included late lung cancer recurrence (6 patients), second primary malignancies (7 patients), cardiopulmonary insufficiency (4 patients), and miscellaneous causes unrelated to cancer and its treatment (7 patients). Long-term survival after pneumonectomy for nonsmall cell lung cancer occurs in 20% of patients. Late lung cancer recurrence and second primary malignancies are important causes of death in these patients. Late cardiopulmonary insufficiency related to adverse physiological consequences of pneumonectomy is uncommon. Long-term follow-up is recommended after pneumonectomy for nonsmall cell lung cancer.
