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Bone marrow-derived progenitor cells in end-stage lung disease patients.

Gilpin SE, Lung K, de Couto GT, Cypel M, Sato M, Singer LG, Keshavjee S, Waddell TK - BMC Pulm Med (2013)

Bottom Line: An increase in CD45⁺Collagen-1⁺ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients.Plasma cytokine levels differed between disease groups, with a significant correlation between SCGF-β and CCSP⁺ cells and between Monocyte Chemotactic Protein-1 and fibrocytes.An increase in the novel CCSP⁺ epithelial-like progenitors in cystic fibrosis patients was found.

View Article: PubMed Central - HTML - PubMed

Affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, North Wing, 9N - 949, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada.

ABSTRACT

Background: Chronic lung diseases are marked by progressive inflammation, tissue damage and remodelling. Bone marrow-derived progenitor cells may contribute to these processes. The objectives of this study were to (1) to quantify CD45⁺Collagen-1⁺ fibrocytes and a novel epithelial-like population of bone marrow-derived cells, which express Clara Cell Secretory Protein, in patients at the time of lung transplant and (2) to evaluate mediators that may act to recruit these cells during injury.

Methods: Using an observational design, progenitor cells were quantified by flow cytometry from both bone marrow (BM) and peripheral blood (PB). Migration was tested using in vitro transwell assays. Multiplex bead-based assays were used to quantify plasma cytokines.

Results: An increase in CD45⁺Collagen-1⁺ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients. Cystic fibrosis patients had an increase in CCSP⁺ cells in both the BM and PB. The proportion of CCSP⁺ cells in the BM and PB was correlated. CCSP+ cells express the chemokine receptors CCR2, CCR4, CXCR3, and CXCR4, and significantly migrated in vitro toward Stromal Derived Factor-1 (SDF-1) and Stem Cell Growth Factor-β (SCGF-β). Plasma cytokine levels differed between disease groups, with a significant correlation between SCGF-β and CCSP⁺ cells and between Monocyte Chemotactic Protein-1 and fibrocytes.

Conclusions: Different bone marrow-derived cells are found in various lung diseases. Increased fibrocytes were associated with fibrotic lung diseases. An increase in the novel CCSP⁺ epithelial-like progenitors in cystic fibrosis patients was found. These differences may be mediated by alterations in plasma cytokines responsible for cell recruitment.

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Plasma cytokine concentrations in end-stage lung disease patients. Comparison of plasma cytokine concentrations between cystic fibrosis (CF) (n = 19), chronic obstructive pulmonary disease (COPD) (n = 16), and pulmonary fibrosis patients (PF) (n = 17) compared to lung donor and healthy volunteer controls (n = 18). Statistically significant differences were found for (A) Interferon gamma-induced protein 10 (IP-10), (B) Monocyte Chemotactic Protein-1 (MCP-1) (C) Monokine-Induced by Gamma Interferon (MIG), and (D) Macrophage Migration Inhibitory Factor (MIF) levels. Kruskal-Wallis test with Dunn’s multiple comparison post-hoc analysis. Boxes show the median, 25th and 75th percentiles. Whiskers represent the 2.5 and 97.5 percentiles.
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Figure 7: Plasma cytokine concentrations in end-stage lung disease patients. Comparison of plasma cytokine concentrations between cystic fibrosis (CF) (n = 19), chronic obstructive pulmonary disease (COPD) (n = 16), and pulmonary fibrosis patients (PF) (n = 17) compared to lung donor and healthy volunteer controls (n = 18). Statistically significant differences were found for (A) Interferon gamma-induced protein 10 (IP-10), (B) Monocyte Chemotactic Protein-1 (MCP-1) (C) Monokine-Induced by Gamma Interferon (MIG), and (D) Macrophage Migration Inhibitory Factor (MIF) levels. Kruskal-Wallis test with Dunn’s multiple comparison post-hoc analysis. Boxes show the median, 25th and 75th percentiles. Whiskers represent the 2.5 and 97.5 percentiles.

Mentions: When the plasma protein concentrations were compared across the 3 main end-stage lung diseases, different patterns of expression were noted for some key inflammatory cytokines. Specifically, it was found that IP-10 and MCP-1 are increased in IPF patients, while MIG is increased in across all 3 end-stage groups, and MIF is specifically increased in CF patients when each were compared to lung donor and healthy volunteer control plasma (Figure 7A-D).


Bone marrow-derived progenitor cells in end-stage lung disease patients.

Gilpin SE, Lung K, de Couto GT, Cypel M, Sato M, Singer LG, Keshavjee S, Waddell TK - BMC Pulm Med (2013)

Plasma cytokine concentrations in end-stage lung disease patients. Comparison of plasma cytokine concentrations between cystic fibrosis (CF) (n = 19), chronic obstructive pulmonary disease (COPD) (n = 16), and pulmonary fibrosis patients (PF) (n = 17) compared to lung donor and healthy volunteer controls (n = 18). Statistically significant differences were found for (A) Interferon gamma-induced protein 10 (IP-10), (B) Monocyte Chemotactic Protein-1 (MCP-1) (C) Monokine-Induced by Gamma Interferon (MIG), and (D) Macrophage Migration Inhibitory Factor (MIF) levels. Kruskal-Wallis test with Dunn’s multiple comparison post-hoc analysis. Boxes show the median, 25th and 75th percentiles. Whiskers represent the 2.5 and 97.5 percentiles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750607&req=5

Figure 7: Plasma cytokine concentrations in end-stage lung disease patients. Comparison of plasma cytokine concentrations between cystic fibrosis (CF) (n = 19), chronic obstructive pulmonary disease (COPD) (n = 16), and pulmonary fibrosis patients (PF) (n = 17) compared to lung donor and healthy volunteer controls (n = 18). Statistically significant differences were found for (A) Interferon gamma-induced protein 10 (IP-10), (B) Monocyte Chemotactic Protein-1 (MCP-1) (C) Monokine-Induced by Gamma Interferon (MIG), and (D) Macrophage Migration Inhibitory Factor (MIF) levels. Kruskal-Wallis test with Dunn’s multiple comparison post-hoc analysis. Boxes show the median, 25th and 75th percentiles. Whiskers represent the 2.5 and 97.5 percentiles.
Mentions: When the plasma protein concentrations were compared across the 3 main end-stage lung diseases, different patterns of expression were noted for some key inflammatory cytokines. Specifically, it was found that IP-10 and MCP-1 are increased in IPF patients, while MIG is increased in across all 3 end-stage groups, and MIF is specifically increased in CF patients when each were compared to lung donor and healthy volunteer control plasma (Figure 7A-D).

Bottom Line: An increase in CD45⁺Collagen-1⁺ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients.Plasma cytokine levels differed between disease groups, with a significant correlation between SCGF-β and CCSP⁺ cells and between Monocyte Chemotactic Protein-1 and fibrocytes.An increase in the novel CCSP⁺ epithelial-like progenitors in cystic fibrosis patients was found.

View Article: PubMed Central - HTML - PubMed

Affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, North Wing, 9N - 949, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada.

ABSTRACT

Background: Chronic lung diseases are marked by progressive inflammation, tissue damage and remodelling. Bone marrow-derived progenitor cells may contribute to these processes. The objectives of this study were to (1) to quantify CD45⁺Collagen-1⁺ fibrocytes and a novel epithelial-like population of bone marrow-derived cells, which express Clara Cell Secretory Protein, in patients at the time of lung transplant and (2) to evaluate mediators that may act to recruit these cells during injury.

Methods: Using an observational design, progenitor cells were quantified by flow cytometry from both bone marrow (BM) and peripheral blood (PB). Migration was tested using in vitro transwell assays. Multiplex bead-based assays were used to quantify plasma cytokines.

Results: An increase in CD45⁺Collagen-1⁺ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients. Cystic fibrosis patients had an increase in CCSP⁺ cells in both the BM and PB. The proportion of CCSP⁺ cells in the BM and PB was correlated. CCSP+ cells express the chemokine receptors CCR2, CCR4, CXCR3, and CXCR4, and significantly migrated in vitro toward Stromal Derived Factor-1 (SDF-1) and Stem Cell Growth Factor-β (SCGF-β). Plasma cytokine levels differed between disease groups, with a significant correlation between SCGF-β and CCSP⁺ cells and between Monocyte Chemotactic Protein-1 and fibrocytes.

Conclusions: Different bone marrow-derived cells are found in various lung diseases. Increased fibrocytes were associated with fibrotic lung diseases. An increase in the novel CCSP⁺ epithelial-like progenitors in cystic fibrosis patients was found. These differences may be mediated by alterations in plasma cytokines responsible for cell recruitment.

Show MeSH
Related in: MedlinePlus