PMID- 22542910 OWN - NLM STAT- MEDLINE DCOM- 20121012 LR - 20121115 IS - 1872-7603 (Electronic) IS - 0165-0378 (Linking) VI - 94 IP - 2 DP - 2012 Jun TI - Trophoblast debris modulates the expression of immune proteins in macrophages: a key to maternal tolerance of the fetal allograft? PG - 131-41 LID - 10.1016/j.jri.2012.03.488 [doi] AB - Interactions between maternal immune cells and the placenta are of substantial interest since diseases of pregnancy, such as recurrent miscarriage, villitis of unknown etiology and preeclampsia may arise due to inadequate adaptation of the maternal immune system. During normal pregnancy trophoblast debris is shed from the placenta into the maternal blood in large quantities. This trophoblast debris is then rapidly cleared from the maternal circulation. In this study, we exposed trophoblast debris generated from an in vitro placental explant model to peripheral blood-derived macrophages and quantified a variety of molecules that are important in immune responses by ELISA or flow cytometry. Phagocytosis of trophoblast debris resulted in reduced cell-surface expression of MHC-II molecules, the costimulatory molecules (CD80, CD86, CD40 and B7H3), monocyte chemoattractant protein-1 (MCP-1), inter-cellular adhesion molecule 1 (ICAM-1) and IL-8 receptors in macrophages while the expression of programmed death-1 ligand 1 (PD-L1) was upregulated. In addition, phagocytosis of trophoblast debris induced the secretion of the anti-inflammatory cytokines IL-10, IL6 and IL1Ra and decreased the secretion of pro-inflammatory cytokines IL-1beta, IL12p70 and IL-8 by macrophages. Phagocytosis of trophoblast debris also increased macrophage expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO). We have shown that phagocytosis of trophoblast debris from normal placentae alters the phenotype of macrophages such that they are likely to deviate maternal immune responses towards tolerance and away from inflammation. This may be one of the mechanisms that allow the human fetal allograft to survive in direct contact with the maternal immune system. CI - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved. FAU - Abumaree, M H AU - Abumaree MH AD - King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, National Guard Health Affairs, P.O. Box 22490, Riyadh 11426, Mail Code 1515, Saudi Arabia. abumareem@ksau-hs.edu.sa FAU - Chamley, L W AU - Chamley LW FAU - Badri, M AU - Badri M FAU - El-Muzaini, M F AU - El-Muzaini MF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120427 PL - Ireland TA - J Reprod Immunol JT - Journal of reproductive immunology JID - 8001906 RN - 0 (Antigens, CD) RN - 0 (Cytokines) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) RN - 0 (Inflammation Mediators) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Antigens, CD/genetics/metabolism MH - Cells, Cultured MH - Cellular Structures/cytology/*immunology/metabolism MH - Cytokines/genetics/metabolism MH - Female MH - Fetus/*immunology MH - Gene Expression Regulation, Developmental/immunology MH - Histocompatibility Antigens Class II/genetics/metabolism MH - Humans MH - Immune Tolerance MH - Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/metabolism MH - Inflammation Mediators/metabolism MH - Intercellular Adhesion Molecule-1/genetics/metabolism MH - Macrophages/*immunology MH - Placental Circulation/immunology MH - Pregnancy MH - *Transplantation Tolerance MH - Transplantation, Homologous/*immunology MH - Trophoblasts/cytology/*immunology/metabolism EDAT- 2012/05/01 06:00 MHDA- 2012/10/13 06:00 CRDT- 2012/05/01 06:00 PHST- 2011/11/04 00:00 [received] PHST- 2012/03/19 00:00 [revised] PHST- 2012/03/26 00:00 [accepted] PHST- 2012/05/01 06:00 [entrez] PHST- 2012/05/01 06:00 [pubmed] PHST- 2012/10/13 06:00 [medline] AID - S0165-0378(12)00556-6 [pii] AID - 10.1016/j.jri.2012.03.488 [doi] PST - ppublish SO - J Reprod Immunol. 2012 Jun;94(2):131-41. doi: 10.1016/j.jri.2012.03.488. Epub 2012 Apr 27.