Mechanisms of anti-GPIbα antibody-induced thrombocytopenia in mice.

Blood
Yosuke MorodomiTaisuke Kanaji

Abstract

Immune thrombocytopenia (ITP) is an acquired bleeding disorder characterized by antibody-mediated platelet destruction. Different mechanisms have been suggested to explain accelerated platelet clearance and impaired thrombopoiesis, but the pathophysiology of ITP has yet to be fully delineated. In this study, we tested 2 mouse models of immune-mediated thrombocytopenia using the rat anti-mouse GPIbα monoclonal antibody 5A7, generated in our laboratory. After a single IV administration of high-dose (2 mg/kg) 5A7, opsonized platelets were rapidly cleared from the circulation into the spleen and liver; this was associated with rapid upregulation of thrombopoietin (TPO) messenger RNA. In contrast, subcutaneous administration of low-dose 5A7 (0.08-0.16 mg/kg) every 3 days gradually lowered the platelet count; in this case, opsonized platelets were observed only in the spleen, and TPO levels remained unaltered. Interestingly, in both models, the 5A7 antibody was found on the surface of, as well as internalized to, bone marrow megakaryocytes. Consequently, platelets generated in the chronic phase of repeated subcutaneous 5A7 administration model showed reduced GPIbα membrane expression on their surface. Our findings indicate that evalu...Continue Reading

References

Oct 24, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alessandra WarrenPatrick Bertolino
Dec 9, 2014·Nature Medicine·Renata GrozovskyKarin M Hoffmeister
May 13, 2015·The Journal of Cell Biology·Satoshi NishimuraRyozo Nagai
Apr 19, 2017·Blood·Michele P Lambert, Terry B Gernsheimer
Jul 19, 2017·Proceedings of the National Academy of Sciences of the United States of America·Yun LiLijun Xia
Jul 18, 2018·Current Opinion in Hematology·June LiHeyu Ni
Aug 15, 2018·Proceedings of the National Academy of Sciences of the United States of America·Taisuke KanajiPaul Schimmel
Dec 19, 2019·Journal of Blood Medicine·Jaleah HawkinsBrian R Curtis
Jan 29, 2020·Research and Practice in Thrombosis and Haemostasis·Yosuke MorodomiTaisuke Kanaji

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Citations

Jun 20, 2020·Blood·Karin M Hoffmeister
May 13, 2021·Research and Practice in Thrombosis and Haemostasis·Danielle KarakasHeyu Ni
Oct 16, 2021·Journal of Thrombosis and Haemostasis : JTH·Wariya SanrattanaCoen Maas

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