Coexpression of myofibroblast and macrophage markers: novel evidence for an in vivo plasticity of chorioamniotic mesodermal cells of the human placenta

Abstract

Human chorioamniotic membranes generate temporary but large mucosal surfaces. Due to lack of fetal vessels, macrophages represent the only subset of immunocytes of fetal origin available in the chorioamniotic mesodermal layer. This layer contains two distinct groups of cells: the fibroblasts/myofibroblasts and the macrophages; however, the relative contribution of these two cell populations has been a point of contention. In addressing various discrepancies, we hypothesized that cells in the chorioamniotic mesodermal layer have plasticity. Immunophenotyping of these cells using a panel of antibodies (CD14, CD68, CD163, HLA-DR, type I procollagen, alpha-smooth muscle actin, desmin, vimentin) revealed coexpression of both myofibroblast and macrophage markers. The proportion of CD14+ macrophages was higher in inflamed chorioamniotic membranes (P<0.05). Cells immunoreactive to the macrophage markers showed nuclear expression of PU.1, a hematopoietic cell-specific transcription factor. Furthermore, treatment with proinflammatory cytokines (IL-1beta and TNFalpha) or Toll-like receptor-4 overexpression upregulated PU.1 mRNA expression in chorioamniotic mesodermal cells. Overexpression of PU.1 in chorionic mesodermal cells increased the expression of CD14 mRNA and protein. A reporter gene assay and chromatin immunoprecipitation demonstrated binding of PU.1 to the CD14 promoter region. This study reports that chorioamniotic mesodermal cells display plasticity ranging from overt transformation of fibroblast/myofibroblast to macrophages, and that PU.1 plays a role in macrophage differentiation. Chorioamniotic mesodermal cells are another novel example of phenotypic switching between fibroblast/myofibroblast and macrophage. The findings reported herein suggest that the plasticity of mesodermal cells is an effective mechanism of the chorioamniotic membranes to manage several biological needs, such as mucosal immune defense and the maintenance/disruption of physical integrity, with a limited pool of cells.