Viall 2013 J Autoimmun

From Bioblast
Publications in the MiPMap
Viall CA, Chen Q, Liu B, Hickey A, Snowise S, Salmon JE, Stone PR, Chamley LW (2013) Antiphospholipid antibodies internalised by human syncytiotrophoblast cause aberrant cell death and the release of necrotic trophoblast debris. J Autoimmun 47:45-57.

Β» PMID: 240351196

Viall CA, Chen Q, Liu B, Hickey A, Snowise S, Salmon JE, Stone PR, Chamley LW (2013) J Autoimmun

Abstract: Antiphospholipid antibodies (aPL) are the strongest maternal risk factor for pre-eclampsia, a hypertensive disease of human pregnancy. Pre-eclampsia is triggered by a toxic factor released from the placenta that activates the maternal endothelium. Antiphospholipid antibodies cause the release of necrotic trophoblast debris from the placental syncytiotrophoblast and this debris can activate endothelial cells. In this study, we investigated how aPL affects syncytiotrophoblast death and production of necrotic trophoblast debris by examining the interaction between aPL and human first trimester placental explants. Human polyclonal and murine monoclonal aPL, but not control antibodies, were rapidly internalised by the syncytiotrophoblast. Inhibitors of endocytosis or the low-density lipoprotein receptor (LDLR) family, but not toll-like receptors, decreased the internalisation of aPL and prevented the release of necrotic trophoblast debris from the syncytiotrophoblast. Once internalised, aPL increased inner mitochondrial membrane leak and Cytochrome c release while depressing oxidative flux through Complex IV of the electron transport system in syncytiotrophoblast mitochondria. These data suggest that the human syncytiotrophoblast internalises aPL by antigen-dependent endocytosis involving LDLR family members. Once internalised by the syncytiotrophoblast, aPL affects the death-regulating mitochondria, causing extrusion of necrotic trophoblast debris which can activate maternal endothelial cells thereby contributing to the pathogenesis of pre-eclampsia. β€’ Keywords: Antiphospholipid antibody, Autoantibody penetration, LDLR homolog, Mitochondria, Placenta, Pre-eclampsia

β€’ O2k-Network Lab: NZ Auckland Hickey AJ, CN Beijing Chen Q

Labels: MiParea: Respiration, mt-Medicine 

Organism: Human  Tissue;cell: Genital 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S  HRR: Oxygraph-2k 


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