Identification of a novel neutrophil population: proangiogenic granulocytes in second-trimester human decidua

Hagai Amsalem1, Melissa Kwan2, Aleah Hazan2

  • 1Research 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;

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.

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