title: Human extravillous trophoblasts bind but do not internalize antiphospholipid antibodies.
abstract: Obstetric morbidity in women with antiphospholipid antibodies (aPLs) may reflect the adverse effects of aPLs on placental cells such as extravillous trophoblasts and the syncytiotrophoblast. Antiphospholipid antibodies may affect the syncytiotrophoblast after being internalised by members of the Low-density lipoprotein receptor (LDLR) family and the antigen of aPLs, β2 glycoprotein I.
  
  
  
  This study aimed to determine whether aPL internalization was a mechanism by which aPLs adversely affect extravillous trophoblasts.
  
  
  
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  Fluorescently-labelled monoclonal aPLs IIC5 or ID2 were incubated with first trimester extravillous trophoblast outgrowths and visualized by microscopy. The subcellular expression of β2 glycoprotein I and LDLR family members was investigated by live/permeabilised immunocytochemistry.
  
  
  
  Unlike the syncytiotrophoblast of anchoring villi, monoclonal aPLs were not internalised by extravillous trophoblasts, which expressed LDLR family members intracellularly. The aPL IIC5 bound to the surface of extravillous trophoblasts in a pattern similar to the extracellular expression of β2 glycoprotein I.
  
  
  
  The mechanisms of action of aPLs are different in extravillous trophoblasts and the syncytiotrophoblast. The interaction of aPLs with the extravillous trophoblast surface, which may involve β2 glycoprotein I, is consistent with reports that aPLs trigger intracellular signaling cascades through cell-surface receptors.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, New Zealand. Electronic address: chez.viall@gmail.com.
authors.forename: Chez A
authors.initials: CA
authors.lastname: Viall
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, New Zealand; Hospital of Obstetrics and Gynaecology, Fudan University, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, New Zealand; Gravida: National Centre for Growth and Development, New Zealand.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Stone
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, New Zealand; Gravida: National Centre for Growth and Development, New Zealand.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Chamley
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D006801:Humans; D010920:Placenta / Q000187:drug effects* / Q000276:immunology; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D014327:Trophoblasts / Q000187:drug effects* / Q000276:immunology
chemical_list: D017152:Antibodies, Antiphospholipid
keywords: Antiphospholipid antibody; Extravillous trophoblast; Placenta; Pregnancy