title: Infusion of bone marrow mononuclear cells reduces lung fibrosis but not inflammation in the late stages of murine silicosis.
abstract: We hypothesized that infusion of bone marrow mononuclear cells (BMMCs) in the late stages of silica-induced damage would reduce the remodelling process in a murine model of silicosis. C57BL/6 mice were assigned to 2 groups. In the SIL group, mice were instilled with a silica particle suspension intratracheally. Control (C) mice received saline under the same protocol. On the 40th day, some of the animals from both groups were killed. The others were treated with either saline or BMMCs (1×10(6) cells) intravenously (C+BMMC and SIL+BMMC), and the mice were killed 70 days after the start of the protocol. In the mice in the SIL+BMMC group, collagen deposition, the presence of silica particles inside nodules, the presence of macrophages and cells reactive for inducible nitric oxide synthase were reduced. Lung parameters also improved. Beyond that, the total and differential cellularity of bronchoalveolar lavage fluid, immunoexpression of transforming growth factor-β, the number of T regulatory cells and apoptosis were increased. However, the presence of male donor cells in lung tissue was not observed using GFP+ cells (40d) or Y chromosome DNA (70d). Therefore, BMMC therapy in the late stages of experimental silicosis improved lung function by diminishing fibrosis but inflammatory cells persisted, which could be related to expansion of T regulatory cells, responsible for the beneficial effects of cell therapy.
authors.affiliation: Laboratory of Cellular Pathology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Cellular and Molecular Physiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Pulmonary Investigation, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Miquéias
authors.initials: M
authors.lastname: Lopes-Pacheco
authors.affiliation: Laboratory of Cellular Pathology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Túlio G
authors.initials: TG
authors.lastname: Ventura
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Helena D'Anunciação
authors.initials: HD
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Cellular Pathology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Leonardo C
authors.initials: LC
authors.lastname: Monção-Ribeiro
authors.affiliation: Department of Radiology, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bianca
authors.initials: B
authors.lastname: Gutfilen
authors.affiliation: Department of Radiology, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Sergio A L
authors.initials: SA
authors.lastname: de Souza
authors.affiliation: Laboratory of Pulmonary Investigation, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Patrícia R M
authors.initials: PR
authors.lastname: Rocco
authors.affiliation: Laboratory of Cellular Pathology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Cellular Proliferation and Differentiation, Biomedical Science Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
authors.affiliation: Laboratory of Cellular Pathology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Takiya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016026:Bone Marrow Transplantation; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000637:transplantation; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D012822:Silicon Dioxide / Q000633:toxicity; D012829:Silicosis / Q000473:pathology / Q000628:therapy*
chemical_list: D012822:Silicon Dioxide