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

Cited 26 time in Web of Science Cited 25 time in Scopus
Issue Date
2008-01-30
Publisher
Nature Publishing Group
Citation
Lab Invest. 2008;88(4):365-374
Keywords
Antigens, CD14/metabolismBiological Markers/metabolismCell Differentiation/*physiologyExtraembryonic Membranes/*cytology/immunology/metabolismFibroblasts/*cytologyHumansImmunophenotypingMacrophages/*cytologyMesoderm/*cytology/metabolism/physiologyPlacenta/cytology/immunology/metabolismPromoter Regions, GeneticProto-Oncogene Proteins/metabolismTrans-Activators/metabolism
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.
ISSN
1530-0307 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18227805

http://www.nature.com/labinvest/journal/v88/n4/pdf/3700749a.pdf

https://hdl.handle.net/10371/68065
DOI
https://doi.org/10.1038/labinvest.3700749
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College of Medicine/School of Medicine (의과대학/대학원)Obstetrics & Gynecology (산부인과전공)Journal Papers (저널논문_산부인과학전공)
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