Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage.

The Journal of Clinical Investigation
Issaka YougbaréHeyu Ni

Abstract

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening disease in which intracranial hemorrhage (ICH) is the major risk. Although thrombocytopenia, which is caused by maternal antibodies against β3 integrin and occasionally by maternal antibodies against other platelet antigens, such as glycoprotein GPIbα, has long been assumed to be the cause of bleeding, the mechanism of ICH has not been adequately explored. Utilizing murine models of FNAIT and a high-frequency ultrasound imaging system, we found that ICH only occurred in fetuses and neonates with anti-β3 integrin-mediated, but not anti-GPIbα-mediated, FNAIT, despite similar thrombocytopenia in both groups. Only anti-β3 integrin-mediated FNAIT reduced brain and retina vessel density, impaired angiogenic signaling, and increased endothelial cell apoptosis, all of which were abrogated by maternal administration of intravenous immunoglobulin (IVIG). ICH and impairment of retinal angiogenesis were further reproduced in neonates by injection of anti-β3 integrin, but not anti-GPIbα antisera. Utilizing cultured human endothelial cells, we found that cell proliferation, network formation, and AKT phosphorylation were inhibited only by murine anti-β3 integrin ant...Continue Reading

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Citations

Nov 14, 2015·Archivum Immunologiae Et Therapiae Experimentalis·Ewa BrojerKrystyna Maślanka
Apr 22, 2016·Cellular and Molecular Life Sciences : CMLS·Yiming Wang, Heyu Ni
Jun 11, 2016·Critical Reviews in Clinical Laboratory Sciences·Xiaohong Ruby XuHeyu Ni
Mar 7, 2017·Thrombosis Research·Lilach Bonstein, Nuhad Haddad
Jun 24, 2017·Expert Review of Hematology·Dian WinkelhorstEnrico Lopriore
Sep 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Aye Myat Myat ThinnJieqing Zhu
Jun 11, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Sentot SantosoUlrich J Sachs
Jul 15, 2015·Oncotarget·Issaka YougbareHeyu Ni
Sep 14, 2017·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Shadi TabibianAkbar Dorgalaleh
Aug 28, 2020·Frontiers in Immunology·Conglei LiHeyu Ni
Oct 8, 2020·Pediatric Research·Olachi J Mezu-Ndubuisi, Akhil Maheshwari
Jan 9, 2020·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·L PorcelijnM de Haas
Nov 3, 2020·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Deepak Sharma, Valentina I Tsibizova
May 13, 2021·Research and Practice in Thrombosis and Haemostasis·Danielle KarakasHeyu Ni
Jul 27, 2021·BMJ Nutrition, Prevention & Health·Yixuan FangJianrong Wang

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Methods Mentioned

BETA
immunoprecipitation
flow cytometry
ELISA
antibody array

Software Mentioned

ImageJ

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