Soluble signals from mechanically disrupted lung tissue induce lung-related gene expression in bone marrow-derived cells in vitro.
Differentiation of bone marrow (BM)-derived cells into lung epithelial cells has been reported in vivo in animal models of lung injury. Most studies have used cytokeratin or surfactant protein expression as markers of BM-to-lung cell differentiation. However, concerns as to whether fusion rather than differentiation is the mechanism involved, verification of BM-derived lung cells, and inconsistent findings with different injury models mean that the differentiation potential of BM-derived cells remains unclear. We used a co-culture system, in which BM cell-lung cell fusion is prevented, to examine the ability of 'damage' signals released from mechanically disrupted lung tissue to induce expression of lung-related genes in BM-derived cells in vitro. BM-derived hematopoietic progenitor cells (BM-HPCs) were co-cultured with mechanically disrupted lung tissue. Liver tissue and medium-only co-cultures were also studied as controls. BM-HPCs differentiated into myeloid cells in culture. BM-HPCs proliferated in response to soluble lung damage signals and differentiated into suspension and adherent populations with dendritic cell and Langerhans cell-like characteristics, respectively. Cytokeratins 7 and 18 and surfactant protein B mRNA expression was either induced or upregulated in the dendritic cell (DC)-like population in lung co-cultures. In contrast, these genes were not induced or up-regulated in medium only or liver co-cultures. Up-regulation of E-cadherin mRNA and protein expression also occurred in response to lung damage signals. These results confirm that signals released from damaged lung tissue can induce lung-related gene expression in BM-derived DC-like cells in the absence of cell fusion.
Field-Corbett
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Institute of Immunology, Biology Department, National University of Ireland Maynooth, Maynooth, Ireland.
O'Dea
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D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002459:Cell Fusion; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000473:pathology / Q000502:physiology; D051379:Mice; D010641:Phenotype
D015415:Biomarkers