Human Plasma Membrane-Derived Vesicles Halt Proliferation and Induce Differentiation of THP-1 Acute Monocytic Leukemia Cells


Ansa-Addo, EA; Lange, S; Stratton, D; Antwi-Baffour, S; Cestari, I; Ramirez, MI; McCrossan, MV; Inal, JM; (2010) Human Plasma Membrane-Derived Vesicles Halt Proliferation and Induce Differentiation of THP-1 Acute Monocytic Leukemia Cells. Journal of immunology (Baltimore, Md, 185 (9). pp. 5236-5246. ISSN 0022-1767 DOI: https://doi.org/10.4049/jimmunol.1001656

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Abstract

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 Ca2+-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-beta receptor antagonist SB-431542 and anti-TGF-beta 1 Ab showed that this was due to TGF-beta 1 carried on PMVs. Although TGF-beta 1 levels have been shown to increase in cell culture supernatants during macrophage differentiation and dendritic cell maturation, the presence of TGF-beta 1 in PMVs is yet to be reported. In this study, to our knowledge we show for the first time that TGF-beta 1 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-beta 1-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. The Journal of Immunology, 2010, 185: 5236-5246.

Item Type: Article
Keywords: GROWTH-FACTOR-BETA, MIGRATION INHIBITORY FACTOR, REGULATORY T-CELLS, VITAMIN-D-RECEPTOR, TGF-BETA, MESSENGER-RNA, MICROVESICLES, MICROPARTICLES, MECHANISMS, RESISTANCE
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 20921526
Web of Science ID: 283248700037
URI: http://researchonline.lshtm.ac.uk/id/eprint/2279

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