title: Myeloid expression of angiotensin-converting enzyme facilitates myeloid maturation and inhibits the development of myeloid-derived suppressor cells.
abstract: 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.
authors.affiliation: 1] Division of Immunology, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA [2] Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Xiao Z
authors.initials: XZ
authors.lastname: Shen
authors.affiliation: 1] Division of Immunology, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA [2] School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Derick
authors.initials: D
authors.lastname: Okwan-Duodu
authors.affiliation: Division of Immunology, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Wendell-Lamar
authors.initials: WL
authors.lastname: Blackwell
authors.affiliation: Division of Immunology, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Frank S
authors.initials: FS
authors.lastname: Ong
authors.affiliation: Division of Immunology, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Tea
authors.initials: T
authors.lastname: Janjulia
authors.affiliation: Division of Immunology, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Bernstein
authors.affiliation: 1] Division of Immunology, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA [2] Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Serhan
authors.initials: S
authors.lastname: Alkan
authors.affiliation: 1] Division of Immunology, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, CA, USA [2] Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Bernstein
mesh_terms: D000818:Animals; D008546:Melanoma, Experimental / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000201:enzymology / Q000502:physiology*; D038042:Myelopoiesis; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010641:Phenotype
chemical_list: D007703:Peptidyl-Dipeptidase A