Platelet-endothelial interactions in inflamed mesenteric venules

Platelet-endothelial interactions in inflamed mesenteric venules
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DOI:
10.1182/blood.v91.4.1318
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发表时间:
1998-02-15
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:
Frenette, PS;Moyna, C;Wagner, DD

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选择素是促进白细胞、血小板之间粘附的膜糖蛋白。和内皮细胞。我们以前已经证明,血小板滚动的P-选择素上表达的刺激内皮细胞。本研究我们希望检测血小板和内皮选择素P-和E-选择素的功能。在炎症过程中介导血小板-内皮相互作用。我们证明,使用活体显微镜检查的小静脉发炎与肿瘤坏死因子-α(TNF-α),静息血小板相互作用与P-和E-选择素和白细胞α(1,3)岩藻糖基转移酶FucT IV和FucT VII不提供血小板与选择素配体活性。我们还表明,凝血酶激活野生型(+/+)血小板后,血小板P-选择素可以介导相互作用的TNF-α诱导的内皮配体。为了评估血小板P-选择素在白细胞向炎症部位募集中的潜在作用,我们用含有巨核细胞前体的野生型(+/+)或P-选择素缺陷型(P-/-)骨髓重建了P-和E-选择素缺陷型(P/E-/-)小鼠的骨髓。通过骨髓移植向P/E-/-小鼠提供+/+血小板不能挽救免疫缺陷表型。提示血小板P-选择素在白细胞募集到炎症部位中不具有活性功能。为了参与炎症或止血反应,血小板可以使用内皮选择素。(C)1998年,美国血液学会。
The selectins are membrane glycoproteins promoting adhesive events between leukocytes, platelets. and endothelial cells. We have previously demonstrated that platelets roll on P-selectin expressed on stimulated endothelium. In this study. we wished to examine the function of both the platelet and endothelial selectins, P- and E-selectins. in mediating platelet-endothelial interactions during inflammation. We demonstrate, using intravital microscopic examination of venules inflamed with tumor necrosis factor-alpha (TNF-alpha), that resting platelets interact with both P- and E-selectins and that the leukocyte alpha(1,3)fucosyltransferases FucT IV and FucT VII do not provide platelets with selectin ligand activity. We also show that after thrombin activation of wild-type (+/+) platelets, platelet P-selectin can mediate interactions on a TNF-alpha-inducible endothelial ligand. To evaluate the potential role of platelet P-selectin in the recruitment of leukocytes to inflammatory sites, we reconstituted the bone marrow of mice deficient in both P- and E-selectins (P/E-/-) with wild-type (+/+) or P-selectin-deficient (P-/-) bone marrow containing megakaryocytic precursors. Providing +/+ platelets to P/E-/- mice by bone marrow transplantation did not rescue the immunodeficient phenotype. suggesting that platelet P-selectin does not have an active function in the recruitment of leukocytes into inflammatory sites. To participate in inflammatory or hemostatic responses, platelets may use the endothelial selectins. (C) 1998 by The American Society of Hematology.