RESUMO
We determined whether microcrystalline cellulose (MCC), a component of pharmaceutical tablets, induces pulmonary changes. In vivo [resistive and viscoelastic pressures (DeltaP(1) and DeltaP(2)), static elastance (E(L))] and in vitro [tissue resistance (R), elastance (E), and hysteresivity (eta)] lung mechanics, histology, and bronchoalveolar lavage fluid (BALF) were analyzed 3h, 24h, and 3, 15 and 30 days after intratracheal instillation of saline (C) or MCC in BALB/c mice. DeltaP(1) increased at 3h, remaining higher than C until day 3, while E(L) and DeltaP(2) increased only at 24h. At 3 days all mechanical parameters returned to baseline. R and E increased only at 24h. MCC increased alveolar collapse and the number of neutrophils in BALF at 3h, until 3 and 15 days, respectively. At 3 days MCC migrate from the airways into the parenchyma, where they were observed until 30 days. In conclusion, microcrystalline cellulose yielded an acute and self-limited inflammation that impaired lung mechanics.
Assuntos
Celulose/efeitos adversos , Excipientes/efeitos adversos , Inflamação/induzido quimicamente , Pulmão/patologia , Pulmão/fisiopatologia , Resistência das Vias Respiratórias/efeitos dos fármacos , Resistência das Vias Respiratórias/fisiologia , Animais , Líquido da Lavagem Broncoalveolar , Inflamação/fisiopatologia , Modelos Lineares , Camundongos , Camundongos Endogâmicos BALB C , Alvéolos Pulmonares/patologia , Atelectasia Pulmonar/induzido quimicamente , Distribuição Aleatória , Mecânica Respiratória , Fatores de TempoRESUMO
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.
