Myeloid expression of angiotensin-converting enzyme facilitates myeloid maturation and inhibits the development of myeloid-derived suppressor cells

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells which accumulate in cancer, infection and chronic inflammation. These cells suppress T-cell function and the immune response. Angiotensin-converting enzyme (ACE) is a peptidase that is now known to regu...

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Bibliographic Details
Published in:Laboratory investigation 2014-05, Vol.94 (5), p.536-544
Main Authors: Shen, Xiao Z, Okwan-Duodu, Derick, Blackwell, Wendell-Lamar, Ong, Frank S, Janjulia, Tea, Bernstein, Ellen A, Fuchs, Sebastien, Alkan, Serhan, Bernstein, Kenneth E
Format: Article
Language:English
Subjects:
angiotensin-converting enzyme
Animals
macrophages
Melanoma, Experimental - enzymology
Melanoma, Experimental - metabolism
Mice
Mice, Inbred C57BL
Myeloid Progenitor Cells - enzymology
Myeloid Progenitor Cells - physiology
myeloid-derived suppressor cells
Myelopoiesis
Peptidyl-Dipeptidase A - metabolism
Phenotype
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Summary:Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells which accumulate in cancer, infection and chronic inflammation. These cells suppress T-cell function and the immune response. Angiotensin-converting enzyme (ACE) is a peptidase that is now known to regulate aspects of myelopoiesis. Here, we show that ACE expression correlates with myeloid maturation in vitro. Forced ACE overexpression in monocytic cells reduces the generation of MDSCs. In vivo, mice with a genetic change resulting in myeloid cell ACE overexpression have reduced numbers of blood and splenic MDSCs in a tumor model and in a model of chronic inflammation induced by complete Freund's adjuvant. In contrast, ACE-null mice produce large numbers of MDSCs during chronic inflammation. Macrophages from mice with myeloid ACE overexpressing are more pro-inflammatory and have more tumor-killing activity than cells from wild-type mice. Thus, manipulating myeloid ACE activity can interfere with MDSC development and the maturation of myeloid cells.
ISSN:0023-6837
1530-0307
DOI:10.1038/labinvest.2014.41