3 results for Abumaree, M

  • An in vitro model of human placental trophoblast deportation/shedding.

    Abumaree, M; Stone, Peter; Chamley, Lawrence (2006)

    Journal article
    The University of Auckland Library

    Deportation of trophoblast shed from the placenta into the maternal circulation was first described over 100 years ago. Despite this, little is known about the quantity or nature of the shed and deported trophoblasts. Neither do we have a clear understanding of the fate of deported trophoblasts nor do we have a clear understanding of their effects on the maternal physiology. This deficiency is largely due to the inaccessibility of deported trophoblasts in vivo. This study aimed to produce a model that would allow us to study deported trophoblasts. We devised a system for culturing placental explants of 12-week gestation in cell culture inserts with a stainless steel mesh bottom that allowed the ready harvesting of shed/deported trophoblasts. Immunohistochemical and morphologic investigations demonstrated that these in vitro shed/deported trophoblasts are similar to those found in vivo and that apoptotic, necrotic and viable trophoblasts were shed from the explants. Inhibiting caspases induced a change from predominantly apoptotic to predominantly necrotic trophoblast shedding. We have devised an in vitro model that allows the collection of shed/deported trophoblasts which will significantly enhance our ability to study these cells. Our preliminary investigations confirm that apoptosis plays an important role in trophoblast shedding/deportation.

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  • Trophoblast deportation: Just a waste disposal system or antigen sharing?

    Chamley, Lawrence; Chen, Qi; Ding, J; Stone, PR; Abumaree, M (2011)

    Journal article
    The University of Auckland Library

    Trophoblast deportation, the removal of trophoblastic debris from the placenta via the maternal blood, was first described over 100 years ago. Deported trophoblastic debris ranges in size from nano-meter scale subcellular particles to large multinucleated syncytial knots. Whether trophoblast deportation has any biological significance remains unclear. However, the (semi) allogeneic fetus must induce maternal tolerance to paternally inherited placental antigens. We propose that the clearance of deported trophoblasts may be a mechanism by which the maternal immune system is maintained in a state of tolerance towards paternal antigens. Using an in vitro model, we have shown that when syncytial knots are shed by an apoptosis-like programmed cell death process, then phagocytosed by macrophages, the macrophages produce a tolerogenic response. However, necrotic syncytial knots, when phagocytosed, appear to be immunostimulatory. We have also shown that endothelial cells are likely to be involved in the clearance of syncytial knots from the pulmonary vessels. Phagocytosis of apoptotic syncytial knots by endothelial cells is silent while phagocytosis of necrotic syncytial knots leads to endothelial cell activation characterised by increased endothelial cell-surface adhesion molecule expression and secretion of IL-6 and TGFβ1. All of these molecules may interact with the maternal immune system to exacerbate any adverse maternal response. We propose that in normal pregnancy clearance of apoptotic syncytial knots is important to maintain maternal immune tolerance to the fetus and that in abnormal pregnancies, especially preeclampsia, clearance of necrotic syncytial knots may contribute to the pathogenesis of that condition.

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  • The effects of apoptotic, deported human placental trophoblast on macrophages: Possible consequences for pregnancy

    Abumaree, M; Stone, Peter; Chamley, Lawrence (2006)

    Journal article
    The University of Auckland Library

    During pregnancy, trophoblasts are shed into maternal blood from the placenta as they die. Trophoblasts are fetal cells and are therefore immunologically foreign to the maternal immune system, but the effects of shed trophoblasts on the maternal immune system are poorly characterized. We have used an in vitro villous explant model to harvest shed trophoblasts. These shed trophoblasts consist of multinucleated syncytial knots as well as mononuclear cells, and approximately 90% are apoptotic as determined by immunostaining with antibodies recognizing activated caspase-3 and the M30 cytokeratin neoepitope. U937 cells phagocytosed the shed apoptotic trophoblasts and, subsequently, secretion of the anti-inflammatory cytokine IL-10 was increased. In contrast, secretion of the proinflammatory cytokine Il-1β by U937 cells was decreased after phagocytosis of apoptotic trophoblasts and the changes in both IL-10 and IL-1β secretion were blocked by co-incubation with the phagocytosis inhibitor cytochalasin B. Shed trophoblasts caused a significant increase also in expression of the, immunosuppressive, tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase. We speculate that the shedding of trophoblasts may not be simply a mechanism the fetus uses to dispose of aged trophoblasts but rather shed apoptotic trophoblasts may provide a chronic source of tolerizing paternally derived antigens to regulate maternal immune responses to the fetus.

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