Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice
Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice
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DOI：
10.1182/blood-2011-05-355628
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发表时间：
2012-02-02
期刊：
影响因子：
20.3
通讯作者：
Hoffmeister, Karin M.
中科院分区：
文献类型：
--
作者：
Jansen, A. J. Gerard;Josefsson, Emma C.;Hoffmeister, Karin M.
当冷冻的血小板再次加热时，它们分泌活性唾液酸酶，包括溶酶体唾液酸酶Neu1，并表达表面Neu3，从血小板血管性血友病因子受体（VWFR）中去除唾液酸，特别是GPIb α亚基。在唾液酸酶抑制剂的存在下，冷冻血小板的恢复和循环大大改善。去乙酰化的VWFR也是金属蛋白酶（MPs）的靶标，因为GPIb α和GPV从冷冻血小板表面被切割。受体脱落被MP抑制剂GM6001抑制，并且不发生在表达失活Adam17的Adam17（Delta Zn/Delta Zn）血小板中。关键的是，在没有mp介导的受体脱落的情况下，脱氮化足以导致血小板从循环中快速清除。因此，血小板VWFR的去脂酰化触发血小板清除，并启动GPIb α和GPV进行mp依赖性切割。（血液，2012;119(5):1263-1273）
When refrigerated platelets are rewarmed, they secrete active sialidases, including the lysosomal sialidase Neu1, and express surface Neu3 that remove sialic acid from platelet von Willebrand factor receptor (VWFR), specifically the GPIb alpha subunit. The recovery and circulation of refrigerated platelets is greatly improved by storage in the presence of inhibitors of sialidases. Desialylated VWFR is also a target for metalloproteinases (MPs), because GPIb alpha and GPV are cleaved from the surface of refrigerated platelets. Receptor shedding is inhibited by the MP inhibitor GM6001 and does not occur in Adam17(Delta Zn/Delta Zn) platelets expressing inactive ADAM17. Critically, desialylation in the absence of MP-mediated receptor shedding is sufficient to cause the rapid clearance of platelets from circulation. Desialylation of platelet VWFR therefore triggers platelet clearance and primes GPIb alpha and GPV for MP-dependent cleavage. (Blood. 2012;119(5): 1263-1273)