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Placental fractalkine mediates adhesion of THP-1 monocytes to villous trophoblast

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Abstract

The chemokine fractalkine (CX3CL1) recently attracted increasing attention in the field of placenta research due to its dual nature, acting both as membrane-bound and soluble forms. While the membrane-bound form mediates flow-resistant adhesion of leukocytes to endothelial and epithelial cells via its corresponding receptor CX3CR1, the soluble form arises from metalloprotease-dependent shedding and bears chemoattractive activity for monocytes, natural killer cells and T cells. In human placenta, fractalkine is expressed at the apical microvillous plasma membrane of the syncytiotrophoblast, which may enable close physical contact with circulating maternal leukocytes. Based on these observations, we tested the hypothesis that fractalkine mediates adhesion of monocytes to the villous trophoblast. Forskolin-induced differentiation and syncytialization of the trophoblast cell line BeWo was accompanied with a substantial upregulation in fractalkine expression and led to increased adhesion of the monocyte cell line THP-1, which preferentially bound to syncytia. Blocking as well as silencing of the fractalkine receptor CX3CR1 proved involvement of the fractalkine/CX3CR1 system in adherence of THP-1 monocytes to villous trophoblast. Pre-incubation of THP-1 monocytes with human recombinant fractalkine as well as silencing of CX3CR1 expression in THP-1 monocytes significantly impaired their adherence to BeWo cells and primary term trophoblasts. The present study suggests fractalkine as another candidate among the panel of adhesion molecules enabling stable interaction between leukocytes and the syncytiotrophoblast.

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Acknowledgments

The authors are indebted to Renate Michelmayr (Department of Obstetrics and Gynaecology, Medical University of Graz, Austria) for her excellent technical assistance in cell isolation and cell culture work. M. Gauster is supported by the Austrian Science Fund (FWF): P23859-B19. The Deutsche Forschungsgemeinschaft (DFG) supported F. Herse (HE6249/1-1).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Institute of Cell Biology, Histology and Embryology, Medical University Graz, Harrachgasse 21/VII, 8010, Graz, Austria

    Monika Siwetz, Monika Sundl, Dagmar Kolb, Berthold Huppertz & Martin Gauster

  2. Center for Medical Research, Medical University Graz, Graz, Austria

    Dagmar Kolb

  3. Department of Obstetrics and Gynaecology, Medical University Graz, Graz, Austria

    Ursula Hiden

  4. Experimental and Clinical Research Center, a Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular Medicine, Berlin, Germany

    Florian Herse

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  1. Monika Siwetz
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  2. Monika Sundl
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Correspondence to Martin Gauster.

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Siwetz, M., Sundl, M., Kolb, D. et al. Placental fractalkine mediates adhesion of THP-1 monocytes to villous trophoblast. Histochem Cell Biol 143, 565–574 (2015). https://doi.org/10.1007/s00418-014-1304-0

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  • DOI: https://doi.org/10.1007/s00418-014-1304-0

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