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Histochemistry and Cell Biology

, Volume 143, Issue 6, pp 565–574 | Cite as

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

  • Monika Siwetz
  • Monika Sundl
  • Dagmar Kolb
  • Ursula Hiden
  • Florian Herse
  • Berthold Huppertz
  • Martin GausterEmail author
Original Paper

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.

Keywords

Placental fractalkine Chemokine Trophoblast Monocyte Adhesion 

Notes

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).

Conflict of interest

The authors declare no conflict of interest.

References

  1. Baczyk D, Drewlo S, Proctor L, Dunk C, Lye S, Kingdom J (2009) Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast. Cell Death Differ 16:719–727CrossRefPubMedGoogle Scholar
  2. Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ (1997) A new class of membrane-bound chemokine with a CX3C motif. Nature 385:640–644CrossRefPubMedGoogle Scholar
  3. Bhavsar PK, Sukkar MB, Khorasani N, Lee KY, Chung KF (2008) Glucocorticoid suppression of CX3CL1 (fractalkine) by reduced gene promoter recruitment of NF-kappaB. FASEB J 22:1807–1816CrossRefPubMedGoogle Scholar
  4. Blaschitz A, Weiss U, Dohr G, Desoye G (2000) Antibody reaction patterns in first trimester placenta: implications for trophoblast isolation and purity screening. Placenta 21:733–741CrossRefPubMedGoogle Scholar
  5. Cammas L, Reinaud P, Dubois O, Bordas N, Germain G, Charpigny G (2005) Identification of differentially regulated genes during elongation and early implantation in the ovine trophoblast using complementary DNA array screening. Biol Reprod 72:960–967CrossRefPubMedGoogle Scholar
  6. Cervar M, Blaschitz A, Dohr G, Desoye G (1999) Paracrine regulation of distinct trophoblast functions in vitro by placental macrophages. Cell Tissue Res 295:297–305CrossRefPubMedGoogle Scholar
  7. D’Haese JG, Friess H, Ceyhan GO (2012) Therapeutic potential of the chemokine-receptor duo fractalkine/CX3CR1: an update. Expert Opin Ther Targets 16:613–618CrossRefPubMedGoogle Scholar
  8. Dudas PL, Sague SL, Elloso MM, Farrell FX (2011) Proinflammatory/profibrotic effects of interleukin-17A on human proximal tubule epithelium. Nephron Exp Nephrol 117:e114–e123CrossRefPubMedGoogle Scholar
  9. Dye JF, Jablenska R, Donnelly JL, Lawrence L, Leach L, Clark P, Firth JA (2001) Phenotype of the endothelium in the human term placenta. Placenta 22:32–43CrossRefPubMedGoogle Scholar
  10. Garcia-Lloret MI, Winkler-Lowen B, Guilbert LJ (2000) Monocytes adhering by LFA-1 to placental syncytiotrophoblasts induce local apoptosis via release of TNF-alpha. A model for hematogenous initiation of placental inflammations. J Leukoc Biol 68:903–908PubMedGoogle Scholar
  11. Gauster M, Hiden U, Blaschitz A, Frank S, Lang U, Alvino G, Cetin I, Desoye G, Wadsack C (2007) Dysregulation of placental endothelial lipase and lipoprotein lipase in intrauterine growth-restricted pregnancies. J Clin Endocrinol Metab 92:2256–2263CrossRefPubMedGoogle Scholar
  12. Gauster M, Siwetz M, Orendi K, Moser G, Desoye G, Huppertz B (2010) Caspases rather than calpains mediate remodelling of the fodrin skeleton during human placental trophoblast fusion. Cell Death Differ 17:336–345CrossRefPubMedGoogle Scholar
  13. Gauster M, Berghold VM, Moser G, Orendi K, Siwetz M, Huppertz B (2011a) Fibulin-5 expression in the human placenta. Histochem Cell Biol 135:203–213CrossRefPubMedGoogle Scholar
  14. Gauster M, Hiden U, van Poppel M, Frank S, Wadsack C, Hauguel-de Mouzon S, Desoye G (2011b) Dysregulation of placental endothelial lipase in obese women with gestational diabetes mellitus. Diabetes 60:2457–2464CrossRefPubMedCentralPubMedGoogle Scholar
  15. Grasso E, Paparini D, Hauk V, Salamone G, Leiros CP, Ramhorst R (2014) Differential migration and activation profile of monocytes after trophoblast interaction. PLoS One 9:e97147CrossRefPubMedCentralPubMedGoogle Scholar
  16. Hannan NJ, Salamonsen LA (2008) CX3CL1 and CCL14 regulate extracellular matrix and adhesion molecules in the trophoblast: potential roles in human embryo implantation. Biol Reprod 79:58–65CrossRefPubMedGoogle Scholar
  17. Hannan NJ, Jones RL, White CA, Salamonsen LA (2006) The chemokines, CX3CL1, CCL14, and CCL4, promote human trophoblast migration at the feto-maternal interface. Biol Reprod 74:896–904CrossRefPubMedGoogle Scholar
  18. Hundhausen C, Schulte A, Schulz B, Andrzejewski MG, Schwarz N, von Hundelshausen P, Winter U, Paliga K, Reiss K, Saftig P, Weber C, Ludwig A (2007) Regulated shedding of transmembrane chemokines by the disintegrin and metalloproteinase 10 facilitates detachment of adherent leukocytes. J Immunol 178:8064–8072CrossRefPubMedGoogle Scholar
  19. Huppertz B, Berghold VM, Kawaguchi R, Gauster M (2012) A variety of opportunities for immune interactions during trophoblast development and invasion. Am J Reprod Immunol 67:349–357CrossRefPubMedGoogle Scholar
  20. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O (1997) Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91:521–530CrossRefPubMedGoogle Scholar
  21. Jauniaux E, Watson AL, Hempstock J, Bao YP, Skepper JN, Burton GJ (2000) Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol 157:2111–2122CrossRefPubMedCentralPubMedGoogle Scholar
  22. Joerink M, Rindsjo E, van Riel B, Alm J, Papadogiannakis N (2011) Placental macrophage (Hofbauer cell) polarization is independent of maternal allergen-sensitization and presence of chorioamnionitis. Placenta 32:380–385CrossRefPubMedGoogle Scholar
  23. Labarrere CA, Bammerlin E, Hardin JW, Dicarlo HL (2014) Intercellular adhesion molecule-1 expression in massive chronic intervillositis: implications for the invasion of maternal cells into fetal tissues. Placenta 35:311–317CrossRefPubMedGoogle Scholar
  24. Pfaff AW, Georges S, Abou-Bacar A, Letscher-Bru V, Klein JP, Mousli M, Candolfi E (2005) Toxoplasma gondii regulates ICAM-1 mediated monocyte adhesion to trophoblasts. Immunol Cell Biol 83:483–489CrossRefPubMedGoogle Scholar
  25. Ramos AJ, Cantero MR, Zhang P, Raychowdhury MK, Green A, MacPhee D, Cantiello HF (2008) Morphological and electrical properties of human trophoblast choriocarcinoma, BeWo cells. Placenta 29:492–502CrossRefPubMedGoogle Scholar
  26. Schwarz N, Pruessmeyer J, Hess FM, Dreymueller D, Pantaler E, Koelsch A, Windoffer R, Voss M, Sarabi A, Weber C, Sechi AS, Uhlig S, Ludwig A (2010) Requirements for leukocyte transmigration via the transmembrane chemokine CX3CL1. Cell Mol Life Sci 67:4233–4248CrossRefPubMedGoogle Scholar
  27. Siwetz M, Blaschitz A, Kremshofer J, Bilic J, Desoye G, Huppertz B, Gauster M (2014) Metalloprotease dependent release of placenta derived fractalkine. Mediat Inflamm 2014:839290CrossRefGoogle Scholar
  28. Szukiewicz D, Kochanowski J, Pyzlak M, Szewczyk G, Stangret A, Mittal TK (2013) Fractalkine (CX3CL1) and its receptor CX3CR1 may contribute to increased angiogenesis in diabetic placenta. Mediat Inflamm 2013:437576CrossRefGoogle Scholar
  29. Szukiewicz D, Kochanowski J, Mittal TK, Pyzlak M, Szewczyk G, Cendrowski K (2014a) Chorioamnionitis (ChA) modifies CX3CL1 (fractalkine) production by human amniotic epithelial cells (HAEC) under normoxic and hypoxic conditions. J Inflamm (Lond) 11:12-9255-11-12. eCollection 2014Google Scholar
  30. Szukiewicz D, Kochanowski J, Mittal TK, Pyzlak M, Szewczyk G, Cendrowski K (2014b) CX3CL1 (fractalkine) and TNFalpha production by perfused human placental lobules under normoxic and hypoxic conditions in vitro: the importance of CX3CR1 signaling. Inflamm Res 63:179–189CrossRefPubMedCentralPubMedGoogle Scholar
  31. Turner SL, Mangnall D, Bird NC, Blair-Zajdel ME, Bunning RA (2010) Effects of pro-inflammatory cytokines on the production of soluble fractalkine and ADAM17 by HepG2 cells. J Gastrointest Liv Dis 19:265–271Google Scholar
  32. Wice B, Menton D, Geuze H, Schwartz AL (1990) Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 186:306–316CrossRefPubMedGoogle Scholar
  33. Wolfe MW (2006) Culture and transfection of human choriocarcinoma cells. Methods Mol Med 121:229–239PubMedGoogle Scholar
  34. Xiao J, Garcia-Lloret M, Winkler-Lowen B, Miller R, Simpson K, Guilbert LJ (1997) ICAM-1-mediated adhesion of peripheral blood monocytes to the maternal surface of placental syncytiotrophoblasts: implications for placental villitis. Am J Pathol 150:1845–1860PubMedCentralPubMedGoogle Scholar
  35. Yang Y, Wang Y, Zeng X, Ma XJ, Zhao Y, Qiao J, Cao B, Li YX, Ji L, Wang YL (2012) Self-control of HGF regulation on human trophoblast cell invasion via enhancing c-Met receptor shedding by ADAM10 and ADAM17. J Clin Endocrinol Metab 97:E1390–E1401CrossRefPubMedGoogle Scholar
  36. Yui J, Garcia-Lloret M, Wegmann TG, Guilbert LJ (1994) Cytotoxicity of tumour necrosis factor-alpha and gamma-interferon against primary human placental trophoblasts. Placenta 15:819–835CrossRefPubMedGoogle Scholar
  37. Zhao S, Gu Y, Fan R, Groome LJ, Cooper D, Wang Y (2010) Proteases and sFlt-1 release in the human placenta. Placenta 31:512–518CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Monika Siwetz
    • 1
  • Monika Sundl
    • 1
  • Dagmar Kolb
    • 1
    • 2
  • Ursula Hiden
    • 3
  • Florian Herse
    • 4
  • Berthold Huppertz
    • 1
  • Martin Gauster
    • 1
    Email author
  1. 1.Institute of Cell Biology, Histology and EmbryologyMedical University GrazGrazAustria
  2. 2.Center for Medical ResearchMedical University GrazGrazAustria
  3. 3.Department of Obstetrics and GynaecologyMedical University GrazGrazAustria
  4. 4.Experimental and Clinical Research Center, a Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrueck Center for Molecular MedicineBerlinGermany

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