P-selectin and platelet clearance

P-selectin and platelet clearance
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DOI:
10.1182/blood.v92.11.4446
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发表时间:
1998-12-01
期刊:
影响因子:
20.3
通讯作者:
Wagner, DD
Wagner, DD
中科院分区:
医学1区
文献类型:
--
作者:
Berger, G;Hartwell, DW;Wagner, DD

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被引文献

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P-选择素是由活化的血小板和内皮细胞表达的白细胞粘附受体。为了评估P-选择素在血小板清除中的可能作用,我们采用了小鼠体内生物素化技术。用N-羟基琥珀酰亚胺生物素灌注野生型和P-选择素缺陷小鼠,用荧光链霉亲和素标记后,通过流式细胞术跟踪生物素化血小板的存活。野生型和P-选择素缺陷型血小板的寿命相同,约为4.7天,表明P-选择素在血小板周转中不起作用。当分离生物素化血小板,用凝血酶活化,并重新注射到小鼠体内时,血小板清除率没有变化。相比之下,储存在4摄氏度的血小板在体内的寿命显着减少,但再次没有显着差异,观察到两种基因型之间。输注的凝血酶活化的血小板迅速失去其表面P-选择素在循环中,这种损失是伴随着同时出现的100 kD的P-选择素片段在血浆中。这一观察结果表明,血小板膜P-选择素通过裂解而脱落。总之,这项研究表明,P-选择素,尽管其结合白细胞,不介导血小板清除。然而,血小板活化时可溶性P-选择素的产生可能在调节白细胞募集或血栓生长方面具有生物学意义。(C)1998年,美国血液学会。
P-selectin is an adhesion receptor for leukocytes expressed by activated platelets and endothelial cells. To assess a possible role of P-selectin in platelet clearance, we adapted an in vivo biotinylation technique in mice. Wild-type and P-selectin-deficient mice were infused with N-hydroxysuccinimido biotin, The survival of biotinylated platelets was followed by flow cytometry after labeling with fluorescent streptavidin. Both wild-type and P-selectin-deficient platelets presented identical life spans of about 4.7 days, suggesting that P-selectin does not play a role in platelet turnover. When biotinylated platelets were isolated, activated with thrombin, and reinjected into mice, the rate of platelet clearance was unchanged. In contrast, storage of platelets at 4 degrees C caused a significant reduction in their life span in vivo but again no significant differences were observed between the two genotypes. The infused thrombin-activated platelets rapidly lost their surface P-selectin in circulation, and this loss was accompanied by the simultaneous appearance of a 100-kD P-selectin fragment in the plasma. This observation suggests that the platelet membrane P-selectin was shed by cleavage. In conclusion, this study shows that P-selectin, despite its binding to leukocytes, does not mediate platelet clearance. However, the generation of a soluble form of P-selectin on platelet activation may have biological implications in modulating leukocyte recruitment or thrombus growth. (C) 1998 by The American Society of Hematology.