Human plasma membrane-derived vesicles halt proliferation and induce differentiation of THP-1 acute monocytic leukemia cells

Ephraim A Ansa-Addo, Sigrun Lange, Dan Stratton, Samuel Antwi-Baffour, Igor Cestari, Marcel I Ramirez, Maria V McCrossan, Jameel M Inal

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42 Citations (Scopus)


Plasma membrane-derived vesicles (PMVs) are small intact vesicles released from the cell surface that play a role in intercellular communication. We have examined the role of PMVs in the terminal differentiation of monocytes. The myeloid-differentiating agents all-trans retinoic acid/PMA and histamine, the inflammatory mediator that inhibits promonocyte proliferation, induced an intracellular Ca(2+)-mediated PMV (as opposed to exosome) release from THP-1 promonocytes. These PMVs cause THP-1 cells to enter G(0)-G(1) cell cycle arrest and induce terminal monocyte-to-macrophage differentiation. Use of the TGF-β receptor antagonist SB-431542 and anti-TGF-β1 Ab showed that this was due to TGF-β1 carried on PMVs. Although TGF-β1 levels have been shown to increase in cell culture supernatants during macrophage differentiation and dendritic cell maturation, the presence of TGF-β1 in PMVs is yet to be reported. In this study, to our knowledge we show for the first time that TGF-β1 is carried on the surface of PMVs, and we confirm the presence within PMVs of certain leaderless proteins, with reported roles in myeloid cell differentiation. Our in vitro findings support a model in which TGF-β1-bearing PMVs, released from promonocytic leukemia cells (THP-1) or primary peripheral blood monocytes on exposure to sublytic complement or after treatment with a differentiation therapy agent, such as all-trans retinoic acid, significantly reduce proliferation of THP-1 cells. Such PMVs also induce the terminal differentiation of primary peripheral blood monocytes as well as THP-1 monocytes.

Original languageEnglish
Pages (from-to)5236-46
Number of pages11
JournalJournal of Immunology
Issue number9
Early online date20 Oct 2010
Publication statusPublished - 1 Nov 2010


  • Apoptosis
  • Blotting, Western
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Membrane
  • Cell Proliferation
  • Cell Separation
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Exocytosis
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Leukemia, Monocytic, Acute
  • Microscopy, Electron, Transmission
  • Monocytes
  • Transforming Growth Factor beta1
  • Journal Article
  • Research Support, Non-U.S. Gov't


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