title: Aspirin-triggered lipoxin prevents antiphospholipid antibody effects on human trophoblast migration and endothelial cell interactions.
abstract: OBJECTIVE
  Antiphospholipid antibodies (aPL) interfere with several physiologic functions of human trophoblasts, including reducing their ability to migrate, decreasing their production of angiogenic factors, and inducing an inflammatory response. This may provide the underlying mechanism by which aPL responses lead to recurrent pregnancy loss or preeclampsia in women with obstetric antiphospholipid syndrome (APS). Although treatment with heparin may reduce the rate of recurrent pregnancy loss, the risk of preeclampsia remains high. Therefore, alternative treatments are needed for the management of pregnant patients with APS. Since aspirin-triggered lipoxins (ATLs) have immune and angiogenic modulatory properties, the objective of this study was to determine the effects of the ATL 15-epi-lipoxin A4 on the function of aPL-altered human trophoblasts in the first trimester of pregnancy.
  
  
  METHODS
  A first-trimester human trophoblast cell line (HTR8) was treated with mouse anti-human β2 -glycoprotein I monoclonal antibodies (aPL) in the presence or absence of the ATL 15-epi-lipoxin A4 . Trophoblast migration and interactions with endometrial endothelial cells were measured using Transwell and coculture assays. Trophoblast secretion of cytokines and angiogenic factors was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Treatment of HTR8 cells with ATL reversed the aPL-induced decrease in trophoblast migration, an effect that appeared to be regulated through restoration of interleukin-6 production. Using a model of spiral artery transformation, aPL and sera from APS patients with pregnancy morbidity disrupted trophoblast-endothelial cell interactions, and treatment with ATL restored the stability of the cocultures. In contrast, ATL treatment did not resolve the proinflammatory and antiangiogenic responses of trophoblasts induced by aPL.
  
  
  CONCLUSIONS
  These findings indicate that ATLs may have some benefits in terms of preventing the effects of aPL on trophoblast function, which raises the possibility of the use of ATLs as an adjuvant therapy in women with aPL.
authors.affiliation: University of Antioquia School of Medicine, Medellín, Colombia, and Yale School of Medicine, New Haven, Connecticut.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Alvarez
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Mulla
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Chamley
authors.forename: Angela P
authors.initials: AP
authors.lastname: Cadavid
authors.forename: Vikki M
authors.initials: VM
authors.lastname: Abrahams
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017152:Antibodies, Antiphospholipid / Q000187:drug effects*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D044045:Lipoxins / Q000494:pharmacology*; D018919:Neovascularization, Physiologic; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D044045:Lipoxins; D053482:beta 2-Glycoprotein I; C040527:lipoxin A4