Infusion of bone marrow mononuclear cells reduces lung fibrosis but not inflammation in the late stages of murine silicosis

PLoS One. 2014 Oct 9;9(10):e109982. doi: 10.1371/journal.pone.0109982. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Bone Marrow Transplantation*
  • Cell- and Tissue-Based Therapy*
  • Disease Models, Animal
  • Inflammation / chemically induced
  • Inflammation / pathology
  • Inflammation / therapy
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / transplantation
  • Mice
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / therapy*
  • Silicon Dioxide / toxicity
  • Silicosis / pathology
  • Silicosis / therapy*

Substances

  • Silicon Dioxide

Grants and funding

This work was supported by grants of FAPERJ, CAPES and CNPq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.