Identification of a Novel Neutrophil Population: Proangiogenic Granulocytes in Second-Trimester Human Decidua

被引:99
作者
Amsalem, Hagai [1 ,2 ]
Kwan, Melissa [1 ,3 ]
Hazan, Aleah [1 ,3 ]
Zhang, Jianhong [1 ]
Jones, Rebecca L. [4 ]
Whittle, Wendy [5 ]
Kingdom, John C. P. [5 ]
Croy, B. Anne [6 ]
Lye, Stephen J. [1 ,3 ,5 ]
Dunk, Caroline E. [1 ,5 ]
机构
[1] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Res Ctr Womens & Infants Hlth, Toronto, ON M5T 3H7, Canada
[2] Hadassah Hebrew Univ Med Ctr, Dept Obstet & Gynecol, IL-91120 Jerusalem, Israel
[3] Univ Toronto, Fac Med, Dept Physiol, Toronto, ON M5S 1A8, Canada
[4] Univ Manchester, St Marys Hosp, Maternal & Fetal Hlth Res Ctr, Manchester M13 9WL, Lancs, England
[5] Univ Toronto, Fac Med, Dept Obstet & Gynaecol, Toronto, ON M5G 1E2, Canada
[6] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6, Canada
基金
以色列科学基金会;
关键词
NATURAL-KILLER-CELLS; LARGE GRANULAR LYMPHOCYTES; COLONY-STIMULATING FACTOR; EARLY HUMAN-PREGNANCY; TROPHOBLAST MIGRATION; NK CELLS; RECEPTOR EXPRESSION; HUMAN-ENDOMETRIUM; CCL3; MIP-1-ALPHA; MENSTRUAL-CYCLE;
D O I
10.4049/jimmunol.1303117
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
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.
引用
收藏
页码:3070 / 3079
页数:10
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