去唾液酸化加速冷藏后的血小板清除，并在小鼠中引发 GPIbα 金属蛋白酶介导的切割。
Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice.
机构信息
Translational Medicine Division, Brigham and Women's Hospital, Harvard Medical School, 1 Blackfan Circle, Boston, MA 02115, USA.
出版信息
Blood. 2012 Feb 2;119(5):1263-73. doi: 10.1182/blood-2011-05-355628. Epub 2011 Nov 18.
Abstract
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 GPIbα 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 GPIbα 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(ΔZn/ΔZn) 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 GPIbα and GPV for MP-dependent cleavage.
摘要
当冷藏的血小板被重新加热时，它们会分泌活性唾液酸酶，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）上去除唾液酸，特别是 GPIbα 亚基。在唾液酸酶抑制剂的存在下储存可大大提高冷藏血小板的恢复和循环。去唾液酸化的 VWFR 也是金属蛋白酶（MPs）的靶标，因为 GPIbα 和 GPV 从冷藏血小板的表面被切割下来。受体脱落被 MPs 抑制剂 GM6001 抑制，在表达无活性 ADAM17 的 Adam17(ΔZn/ΔZn)血小板中不会发生。至关重要的是，在没有 MPs 介导的受体脱落的情况下的去唾液酸化足以导致血小板从循环中迅速清除。因此，血小板 VWFR 的去唾液酸化触发血小板清除，并使 GPIbα 和 GPV 为 MPs 依赖性切割做好准备。
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