Human adenosine deaminase 2 induces differentiation of monocytes into macrophages and stimulates proliferation of T helper cells and macrophages

Andrey V. Zavialov, Eduard Gracia, Nicolas Glaichenhaus, Rafael Franco, Anton V. Zavialov, Gregoire Lauvau

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

ADAs play a pivotal role in regulating the level of adenosine, a signaling molecule controlling a variety of cellular responses by binding to and activating four ADRs. Two enzymes, ADA1 and ADA2, are known to possess ADA activity in humans. Although the structure of ADA1 and its role in lymphocytic activation have been known for a long time, the structure and function of ADA2, a member of ADGF, remain enigmatic. Here, we found that ADA2 is secreted by monocytes undergoing differentiation into macrophages or DCs and that it binds to the cell surface via proteoglycans and ADRs. We demonstrate that ADA1 and ADA2 increase the rate of proliferation of monocyte-activated CD4+ T cells independently of their catalytic activity. We also show that ADA2 induces T cell-dependent differentiation of monocytes into macrophages and stimulates macrophage proliferation. Our discovery of the growth factor-like activity of ADA2 explains clinical observations and suggests that this enzyme could be used as a drug candidate to modulate the immune responses during inflammation and cancer.

Original languageEnglish (US)
Pages (from-to)279-290
Number of pages12
JournalJournal of Leukocyte Biology
Volume88
Issue number2
DOIs
StatePublished - Aug 2010

Fingerprint

Helper-Inducer T-Lymphocytes
Monocytes
Macrophages
T-Lymphocytes
Proteoglycans
Enzymes
Human Activities
Adenosine
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Inflammation
Pharmaceutical Preparations
human CECR1 protein
Neoplasms

Keywords

  • Adaptive immunity
  • Development
  • Innate immunity

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Human adenosine deaminase 2 induces differentiation of monocytes into macrophages and stimulates proliferation of T helper cells and macrophages. / Zavialov, Andrey V.; Gracia, Eduard; Glaichenhaus, Nicolas; Franco, Rafael; Zavialov, Anton V.; Lauvau, Gregoire.

In: Journal of Leukocyte Biology, Vol. 88, No. 2, 08.2010, p. 279-290.

Research output: Contribution to journalArticle

Zavialov, Andrey V. ; Gracia, Eduard ; Glaichenhaus, Nicolas ; Franco, Rafael ; Zavialov, Anton V. ; Lauvau, Gregoire. / Human adenosine deaminase 2 induces differentiation of monocytes into macrophages and stimulates proliferation of T helper cells and macrophages. In: Journal of Leukocyte Biology. 2010 ; Vol. 88, No. 2. pp. 279-290.
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