VPAC1 and VPAC2 receptor knock-down prime macrophages and neutrophils to pro inflammatory responses during early pregnancy

G. CALO, V. HAUK, C. VAN, M. O'DORISIO, R. RAMHORST, J. WASCHEK, C. PÉREZ LEIRÓS

Los Angeles

Simposio; Symposium of VIP, VPAC and related pepetides.; 2019

Symposium of VIP, VPAC and related pepetides.

The maintenance of immune homeostasis at the maternal-placental interface is a dynamic process that involves different populations of leucocytes controlled by trophoblast cells. Macrophages express a predominant M2 alternative activation profile during normal pregnancy whereas neutrophil activation is observed in normal pregnancies, but it is higher in pregnancies complicated by preeclampsia. Vasoactive intestinal peptide (VIP) is produced by trophoblast cells and is proposed to contribute to immune homeostasis at early pregnancy. It displays anti inflammatory effects through binding to high affinity VPAC1 and VPAC2 receptors on macrophages and neutrophils. Our goal was to explore whether macrophages and neutrophils from VPAC1 and VPAC2 KO pregnant mice fail to control pro-inflammatory responses at early pregnancy.Macrophages were isolated from the peritoneum of pregnant C57, either WT, VPAC1 KO or VPAC2 KO mice at day 7.5 or 8.5 of pregnancy and then surface markers or cytokine production was assessed. Neutrophils were isolated from bone marrow, using Ficoll gradient centrifugation and ROS production induced by PMA was analyzed. VPAC2 KO mice present a higher expression of the co-stimulatory molecules MHCII and CD86 (MFI MHCII X±SE: WT:12068±2788; VPAC2 KO:77550±10617 P