Trophoblast-derived exosomes mediate monocyte recruitment and differentiation

Am J Reprod Immunol. 2011 Jan;65(1):65-77. doi: 10.1111/j.1600-0897.2010.00880.x.

Abstract

Introduction: trophoblast cells have been demonstrated to regulate monocyte migration and differentiation, leading to pro-inflammatory profiles. Because trophoblast cells release exosomes with immunoregulatory properties, trophoblast-derived exosomes are proposed to 'educate' monocytes, creating a pro-inflammatory environment.

Method of study: exosomes were isolated from conditioned media of Swan71 cells by ultrafiltration and ultracentrifugation. Exosome-induced migration was assessed using a two-chamber system. Cytokine profiles were defined using cytokine arrays, and mRNA levels of affected cytokines were examined by qRT-PCR and ELISA.

Results: within 20 min, 8-10% of monocytes took up labeled exosomes isolated from Swan71 cells. Trophoblast-derived exosomes increased monocyte migration in a dose-dependent manner and produced significant increases in production of interleukin (IL)-1β, IL-6, Serpin-E1, granulocyte colony-stimulating factor, granulocyte/monocyte colony-stimulating factor, and tumor necrosis factor-α.

Conclusion: this study presents the initial demonstration that trophoblast-derived exosomes are capable of recruiting and 'educating' monocytes to produce pro-inflammatory cytokine/chemokine profiles in a cell-contact-independent manner.

MeSH terms

  • Cell Differentiation / physiology
  • Cell Line
  • Cell Movement / physiology
  • Chemokines / biosynthesis
  • Exosomes / physiology*
  • Female
  • Gene Expression Regulation
  • Granulocyte Colony-Stimulating Factor / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Humans
  • Interleukin-1 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Macrophages / cytology
  • Monocytes / cytology
  • Monocytes / physiology*
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • Pregnancy
  • RNA, Messenger / genetics
  • Trophoblasts / cytology
  • Trophoblasts / physiology*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Chemokines
  • Interleukin-1
  • Interleukin-6
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Granulocyte Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor