Please use this identifier to cite or link to this item:
https://repository.monashhealth.org/monashhealthjspui/handle/1/37276
Title: | CD39 and CD73 activity are protective in a mouse model of antiphospholipid antibody-induced miscarriages. | Authors: | Robson S.C.;Nandurkar H.H.;Peter K.;Sashindranath M.;Cowan P.J.;Samudra A.N.;Dwyer K.M.;Selan C.;Freddi S.;Murray-Segal L.;Nikpour M.;Hickey M.J. | Institution: | (Samudra, Selan, Freddi, Sashindranath, Nandurkar) Australian Centre for Blood Diseases, Central Clinical School, Monash University, Alfred Hospital, Melbourne, Australia (Samudra, Selan, Cowan) Immunology Research Centre, St Vincent's Hospital, Melbourne, Australia (Dwyer) School of Medicine, Faculty of Health, Deakin University, Geelong, Australia (Murray-Segal) St. Vincent's Institute, Melbourne, Australia (Nikpour) St. Vincent's Hospital, University of Melbourne, Australia (Hickey) Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Australia (Peter) Atherothrombosis and Vascular Biology, Baker IDI Heart & Diabetes Institute, Central Clinical School, Monash University, Melbourne, Australia (Robson) Harvard Medical School, Department of Medicine, Division of Gastroenterology, Boston, United States | Issue Date: | 13-Mar-2018 | Copyright year: | 2018 | Publisher: | Academic Press | Place of publication: | United Kingdom | Publication information: | Journal of Autoimmunity. 88 (pp 131-138), 2018. Date of Publication: March 2018. | Journal: | Journal of Autoimmunity | Abstract: | Objective: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder of young adults associated with devastating pregnancy complications (recurrent miscarriages, preeclampsia and low birth weight) and vascular complications including thrombosis. The key components implicated in pathogenesis of APS are the complement cascade and tissue factor (TF) activity causing inflammation and coagulation. Purinergic signalling involving catabolism of ATP to adenosine by cell-surface enzymes CD39 and CD73 has anti-inflammatory and anti-thrombotic effects. We studied whether activities of CD39 and CD73 are important in preventing the development of miscarriages in APS. Method(s): We studied frequency of miscarriages and decidual pathology following passive transfer of human aPL-ab to pregnant wildtype mice, and mice deficient in CD39 and CD73, and also transgenic mice exhibiting 2-3X higher CD39 activity. Result(s): aPL-ab infusion in pregnant CD39-or CD73-knockout mice triggers an increase in miscarriages, associated with increased TF expression and complement deposition as well as elevated oxidative stress and pro-inflammatory TNF-alpha and IL-10 expression within the placental decidua. In contrast, aPL-ab induced miscarriages are prevented in mice over-expressing CD39, with reduced decidual TF expression and C3d deposition, diminished lipid peroxidation (4-hydroxynonenal or 4-HNE positive lipid adducts), and reduced TNF-alpha expression. Conclusion(s): We demonstrate a protective role for CD39 in APS and provide rationale for both the development of endothelial cell-targeted soluble CD39 as a novel therapeutic for APS and analysis of perturbations in the purinergic pathway to explain human disease.Copyright © 2017 Elsevier Ltd | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1016/j.jaut.2017.10.009 | ORCID: | Sashindranath, Maithili; ORCID: http://orcid.org/0000-0002-9712-4784 Hickey, Michael J.; ORCID: http://orcid.org/0000-0003-2354-357X | Link to associated publication: | Click here for full text options | PubMed URL: | 29103803 [http://www.ncbi.nlm.nih.gov/pubmed/?term=29103803] | ISSN: | 0896-8411 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/37276 | Type: | Article | Subjects: | anticoagulation antiinflammatory activity *antiphospholipid syndrome/et [Etiology] article catabolism cell surface comparative study complement deposition controlled study adenosine triphosphate/ec [Endogenous Compound] *CD39 antigen/ec [Endogenous Compound] immunoglobulin G/ec [Endogenous Compound] interleukin 10/ec [Endogenous Compound] interleukin 6/ec [Endogenous Compound] *phospholipid antibody/ec [Endogenous Compound] purinergic receptor/ec [Endogenous Compound] thromboplastin/ec [Endogenous Compound] tumor necrosis factor/ec [Endogenous Compound] animal experiment decidua disease association endothelium cell *enzyme activity female fetus fetus resorption human immunohistochemistry lipid peroxidation male mouse nonhuman oxidative stress priority journal reverse transcription polymerase chain reaction RNA isolation signal transduction *spontaneous abortion/et [Etiology] *spontaneous abortion/pc [Prevention] *5' nucleotidase/ec [Endogenous Compound] adenosine/ec [Endogenous Compound] animal model animal tissue endothelium cell *enzyme activity female fetus fetus resorption human immunohistochemistry lipid peroxidation male mouse nonhuman oxidative stress priority journal reverse transcription polymerase chain reaction RNA isolation signal transduction *spontaneous abortion / *etiology / *prevention anticoagulation antiinflammatory activity animal model animal experiment animal tissue *antiphospholipid syndrome / *etiology Article catabolism cell surface comparative study complement deposition controlled study decidua disease association |
Appears in Collections: | Articles |
Show full item record
Items in Monash Health Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.