Naslov
Clearance of Desialylated Platelets by the Hepatic Asialoglycoprotein Receptor Regulates TPO Homeostasis in Vivo.

Autori
Grozovsky, Renata ; Jurak Begonja, Antonija ; Hartwig, John H ; Hoffmeister, Karin M.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Blood / - , 2012, 2170-2170

Skup
54th American Society of Hematology Meeting

Mjesto i datum
Atlanta (GA), Sjedinjene Američke Države, 08.12.2012. - 11.12.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
thrombopoetin; platelets; syalation; AMR

Sažetak
The human body produces and removes 1011 platelets daily to maintain a normal steady-state platelet count, and the level of production can be greatly increased under conditions of platelet destruction. Here, we provide the experimental evidence that platelets with impaired Siaa2–3Galb1–4GlcNAc (LacNAc) structures are removed by the hepatic asialoglycoprotein receptor Asgr1/2, indicating that survival of platelets is intimately tied to surface glycans. Mice lacking Asgr2 subunit that is necessary to assemble a functional receptor have increased platelet survival (t1/2 = 49.5 ± 2h) compared to wild type mice (t1/2 = 31 ± 4h). Surprisingly, platelets from Asgr2-null mice have diminished surface sialic acid, as evidenced by lectins that bind exposed Gal moieties. Hence, desialylated platelets circulate in Asgr2-null mice. Besides "terminating" platelet circulation, the liver is the main source of thrombopoietin (TPO), the major hormone regulating platelet production. We hypothesized that desialylated platelet uptake by hepatic Asgr1/2 would affects TPO mRNA synthesis and have found that liver tissue from Asgr2-null mice has a 40% decrease in TPO mRNA levels compared to liver tissue from WT mice. In contrast, ST3Gal4-null mice, which have high rates of platelet turnover and increased desialylated platelet uptake by the Asgr2, have a 30% increase in TPO mRNA content in their livers. Both plasma TPO levels and platelet TPO contents are similarly altered in both mutant mice. In contrast, and in agreement with published data, antibody-mediated platelet clearance did not affect hepatic TPO mRNA levels. Taken together, these data show that the clearance of desialylated platelets by the hepatic Asgr1/2 regulates TPO homeostasis in vivo.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA