Soluble Signals from Mechanically Disrupted Lung Tissue Induce Lung-Related Gene Expression in Bone Marrow-Derived Cells in Vitro

Abstract

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.