title: Identification of a novel neutrophil population: proangiogenic granulocytes in second-trimester human decidua.
abstract: The maternal leukocytes of the first-trimester decidua play a fundamental role in implantation and early development of the fetus and placenta, yet little is known regarding the second-trimester decidual environment. Our multicolor flow cytometric analyses of human decidual leukocytes detected an elevation in tissue resident neutrophils in the second trimester. These cells in both human and murine samples were spatially restricted to decidua basalis. In comparison with peripheral blood neutrophils (PMNs), the decidual neutrophils expressed high levels of neutrophil activation markers and the angiogenesis-related proteins: vascular endothelial growth factor-A, Arginase-1, and CCL2, similarly shown in tumor-associated neutrophils. Functional in vitro assays showed that second-trimester human decidua conditioned medium stimulated transendothelial PMN invasion, upregulated VEGFA, ARG1, CCL2, and ICAM1 mRNA levels, and increased PMN-driven in vitro angiogenesis in a CXCL8-dependent manner. This study identified a novel neutrophil population with a physiological, angiogenic role in human decidua.
authors.affiliation: Research Centre for Women's and Infants' Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3H7, Canada; Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Mt. Scopus, Jerusalem 91120, Israel;
authors.forename: Hagai
authors.initials: H
authors.lastname: Amsalem
authors.affiliation: Research Centre for Women's and Infants' Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3H7, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
authors.forename: Melissa
authors.initials: M
authors.lastname: Kwan
authors.affiliation: Research Centre for Women's and Infants' Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3H7, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
authors.forename: Aleah
authors.initials: A
authors.lastname: Hazan
authors.affiliation: Research Centre for Women's and Infants' Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3H7, Canada;
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Maternal and Fetal Health Research Centre, St. Mary's Hospital, The University of Manchester, Manchester M13 9WL, United Kingdom;
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Jones
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 1E2, Canada; and.
authors.forename: Wendy
authors.initials: W
authors.lastname: Whittle
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 1E2, Canada; and.
authors.forename: John C P
authors.initials: JC
authors.lastname: Kingdom
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: B Anne
authors.initials: BA
authors.lastname: Croy
authors.affiliation: Research Centre for Women's and Infants' Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3H7, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 1E2, Canada; and.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lye
authors.affiliation: Research Centre for Women's and Infants' Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3H7, Canada; Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 1E2, Canada; and dunk@lunenfeld.ca.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Dunk
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001119:Arginase / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D003656:Decidua / Q000166:cytology* / Q000276:immunology; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D016209:Interleukin-8 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology; D057705:Transendothelial and Transepithelial Migration; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000906:Antibodies; C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; C573420:ICAM1 protein, human; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D016209:Interleukin-8; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; D019707:Receptors, Chemokine; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; C574619:ARG1 protein, human; D001119:Arginase