title: Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia.
abstract: BACKGROUND
  Pre-eclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality worldwide. It is defined by new onset of hypertension and proteinuria after the 20th week of gestation and characterized by systemic exaggerated inflammatory response. D6 is a chemokines scavenger receptor that binds with high affinity CC chemokines, internalizes and targets the ligands for degradation. It is expressed in trophoblast-derived tissues and prevents excessive placenta leukocyte infiltration.The aim of this study was to investigate the expression and function of D6 in human placentae from pre-eclamptic and healthy pregnant women.
  
  
  RESULTS
  Plasma levels of D6-binding CC chemokines (CCL-2, CCL-3, CCL-4, CCL-7, CCL-11) and pro-inflammatory cytokines (IL-6, TNF-α, CRP) were analyzed in 37 healthy pregnant women and 38 patients with PE by multiplex bead assay. Higher circulating levels of CCL7, CCL11, IL-6, (p<0.0001) and CRP (p<0.05) were observed in PE women compared to controls. Levels of circulating CCL4 were decreased in PE (p<0.001), while no significant differences of CCL2, CCL3 or TNF-α levels were detected. Immunofluorescent staining of placental sections showed higher expression of D6 receptor in the PE syncytiotrophoblast. Confocal and Western blot (WB) analyses revealed a prevalent distribution of D6 in trophoblast cells membranes in PE. Increased activation of D6 intracellular pathway was observed by Western blot analyses of p-LIMK and p-cofilin in trophoblast cell lysates. D6 functional assays showed reduced scavenging of CCL2 in PE cells compared to controls. Since actin filaments spatial assembling is essential for D6 intracellular trafficking and scavenging activity, we investigated by confocal microscopy trophoblast cytoskeleton organization and we observed a dramatic disarrangement in PE compared to controls.
  
  
  CONCLUSIONS
  our results suggest membrane distribution of D6 receptor on trophoblast cell membranes in PE, together with reduced functionality, probably due to cytoskeleton impairment.
authors: Department of Obstetrics and Gynaecology, Fondazione Policlinico Agostino Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors: Chiara
authors: C
authors: Tersigni
authors: Department of Obstetrics and Gynaecology, Fondazione Policlinico Agostino Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors: Fiorella
authors: F
authors: Di Nicuolo
authors: Institute of Physics, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors: Giuseppe
authors: G
authors: Maulucci
authors: Department of Surgical Sciences, Sant'Anna Hospital, Università degli Studi di Torino, Turin, Italy.
authors: Alessandro
authors: A
authors: Rolfo
authors: Department of Surgical Sciences, Sant'Anna Hospital, Università degli Studi di Torino, Turin, Italy.
authors: Domenica
authors: D
authors: Giuffrida
authors: Department of Obstetrics and Gynaecology, Fondazione Policlinico Agostino Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors: Manuela
authors: M
authors: Veglia
authors: Institute of Physics, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors: Marco
authors: M
authors: De Spirito
authors: Department of Obstetrics and Gynaecology, Fondazione Policlinico Agostino Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors: Giovanni
authors: G
authors: Scambia
authors: Department of Surgical Sciences, Sant'Anna Hospital, Università degli Studi di Torino, Turin, Italy.
authors: Tullia
authors: T
authors: Todros
authors: Department of Obstetrics and Gynaecology, Fondazione Policlinico Agostino Gemelli, Università Cattolica Del Sacro Cuore, Rome, Italy.
authors: Nicoletta
authors: N
authors: Di Simone
mesh_terms: D000328:Adult; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000097:blood* / Q000378:metabolism; D015398:Signal Transduction; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult; D000097628:Chemokine Receptor D6
chemical_list: D018925:Chemokines; D016207:Cytokines; D019707:Receptors, Chemokine; C515708:ACKR2 protein, human; D000097628:Chemokine Receptor D6