A novel role for platelet secretion in angiogenesis: mediating bone marrow-derived cell mobilization and homing
A novel role for platelet secretion in angiogenesis: mediating bone marrow-derived cell mobilization and homing
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DOI：
10.1182/blood-2010-08-304808
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发表时间：
2011-04-07
期刊：
影响因子：
20.3
通讯作者：
Byzova, Tatiana V.
中科院分区：
文献类型：
--
作者：
Feng, Weiyi;Madajka, Maria;Byzova, Tatiana V.
血管生成加剧了缺血组织或肿瘤进展过程中的缺氧应激。除了内皮细胞增殖和迁移，血管生成过程需要骨髓源性细胞（BMDC）募集到新血管形成部位。然而，缺氧组织和BM之间的通信机制仍然未知。使用2种缺氧诱导的血管生成模型（缺血性后肢手术和皮下肿瘤生长），我们表明血小板输注促进BMDC动员进入循环，BMDC招募到生长的新血管，肿瘤血管形成和缺血肢体的血流恢复，而血小板耗竭抑制这些作用。因此，血小板是BMDC募集到缺血诱导的血管系统中所必需的。血小板α-颗粒的分泌，但致密颗粒和血小板聚集都不是BMDC归巢和随后的血管生成的关键，如使用VAMP-8（-/-）、Pearl和整联蛋白β 3（-/-）血小板所测定的。最后，血小板隔离肿瘤衍生的促进血管生成和BMDC动员，这是由抗血管生成因子血小板反应蛋白-1平衡。血小板中血小板反应蛋白-1的缺乏导致促血管生成因子和抗血管生成因子的失衡，并加速肿瘤生长和血管形成。我们的数据表明，血小板刺激BMDC归巢的VAMP-8依赖的方式，揭示了以前未知的作用，血小板之间的缺氧组织和骨髓血管生成过程中的关键介质。（血。2011; 117（14）：3893-3902）
Angiogenesis alleviates hypoxic stress in ischemic tissues or during tumor progression. In addition to endothelial cell proliferation and migration, the angiogenic process requires bone marrow-derived cell (BMDC) recruitment to sites of neovascularization. However, the mechanism of communication between hypoxic tissues and the BM remains unknown. Using 2 models of hypoxia-induced angiogenesis (ischemic hindlimb surgery and subcutaneous tumor growth), we show that platelet infusion promotes BMDC mobilization into the circulation, BMDC recruitment into growing neovasculature, tumor vascularization, and blood flow restoration in ischemic limbs, whereas platelet depletion inhibits these effects. Thus, platelets are required for BMDC recruitment into ischemia-induced vasculature. Secretion of platelet alpha-granules, but neither dense granules nor platelet aggregation is crucial for BMDC homing and subsequent angiogenesis, as determined using VAMP-8(-/-), Pearl, and integrin Beta 3(-/-) platelets. Finally, platelets sequester tumor-derived promoters of angiogenesis and BMDC mobilization, which are counterbalanced by the antiangiogenic factor thrombospondin-1. A lack of thrombospondin-1 in platelets leads to an imbalance in proangiogenic and antiangiogenic factors and accelerates tumor growth and vascularization. Our data demonstrate that platelets stimulate BMDC homing in a VAMP-8-dependent manner, revealing a previously unknown role for platelets as key mediators between hypoxic tissues and the bone marrow during angiogenesis. (Blood. 2011; 117(14):3893-3902)