Immature myeloid cells accumulate in mouse placenta and promote angiogenesis.

Abstract

We sought to determine whether CD11b(+)Gr1(+) immature myeloid cells (IMCs), which have been shown to promote tumor angiogenesis, accumulate in the placenta and similarly contribute to blood vessel formation. Experiments were performed on 6- to 8-week-old C57Bl/6J female mice. Placentas from pregnant mice or B16F10 tumors that were subcutaneously implanted were analyzed by flow cytometry and confocal microscopy. To determine the proangiogenic potential of IMCs, Matrigel plug assays were performed. IMCs infiltrate the placenta in the proximity of blood vessels, reaching peak concentration at midpregnancy. When isolated from either placentas or B16F10 melanoma tumors, IMCs actively promoted endothelial cell migration into Matrigel plugs in vivo. Furthermore, placental IMCs, similar to tumor-derived IMCs, expressed matrix metalloproteinase-9 and Bv8, 2 pivotal proangiogenic proteins. IMCs that express matrix metalloproteinase-9 and Bv8 infiltrate placentas of pregnant mice and actively promote angiogenesis. These cells show striking similarity to IMCs that populate malignant tumors.