Requirement of alpha(4)beta(1) and alpha(5)beta(1) integrin expression in bone-marrow-derived progenitor cells in preventing endotoxin-induced lung vascular injury and edema in mice.
Requirement of alpha(4)beta(1) and alpha(5)beta(1) integrin expression in bone-marrow-derived progenitor cells in preventing endotoxin-induced lung vascular injury and edema in mice.
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DOI：
10.1002/stem.241
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发表时间：
2009-12
期刊：
影响因子：
5.2
通讯作者：
Malik, Asrar B.
中科院分区：
文献类型：
--
作者：
Wary, Kishore K.;Vogel, Stephen M.;Garrean, Sean;Zhao, Yidan D.;Malik, Asrar B.
本研究的目的是确定整合素介导的骨髓源性祖细胞（BMPC）粘附的作用，作为肺损伤模型中内皮屏障保护的必要条件。使用C57 BL小鼠作为BMPC的来源，其特征在于CD 34+和胎肝激酶-1（Flk 1）+，并且还表达整联蛋白库。我们使用细菌脂多糖（LPS）诱导的肺血管损伤和水肿形成的小鼠模型来测试BMPC整合素表达在防止内皮屏障损伤中的作用。BMPCs与纯化的细胞外基质蛋白的粘附以α4和α5整合素依赖的方式诱导粘着斑激酶（Fak）磷酸化和分支点结构的形成。表达红色荧光蛋白（RFP）的BMPC通过眼眶后静脉途径给予腹腔内注射LPS（7.5 mg/kg体重）的小鼠。我们观察到RFP标记的Flk 1+和CD 34 + BMPC在LPS损伤小鼠中的保留增加长达8周。BMPC移植增加了50%的存活率（在LPS后72-96小时），并减少了LPS诱导的肺血管损伤和血管外含水量。然而，用抗α4或抗α5整合素抗体阻断或shRNA介导的α4或α5整合素沉默在供体BMPC中不能防止血管损伤或水肿形成和死亡。因此，在LPS诱导的急性肺损伤小鼠模型中，肺组织中BMPC的α4和α5整合素依赖性粘附在预防肺血管损伤和增加存活率方面起着关键作用。
The goal of this study was to determine the role of integrin-mediated adhesion of bone-marrow-derived progenitor cells (BMPCs) as a requirement for the endothelial barrier protection in a lung injury model. C57BL mice were used as the source for BMPCs, which were characterized as CD34+ and fetal liver kinase-1 (Flk1)+ and also an expression of a repertoire of integrins. We used a mouse model of bacterial lipopolysaccharide (LPS)-induced lung vascular injury and edema formation to test the effects of BMPC integrin expression in preventing endothelial barrier injury. Adhesion of BMPCs to purified extracellular matrix proteins induced focal adhesion kinase (Fak) phosphorylation and formation of branching point structures in a α4 and α5 integrin-dependent manner. BMPCs expressing red fluorescent protein (RFP) were administered via the retro-orbital venous route in mice treated intraperitonially with LPS (7.5 mg/kg body weight). We observed increased retention of RFP-labeled Flk1+ and CD34+ BMPCs for up to 8 weeks in mice injured with LPS. BMPC transplantation increased survival by 50% (at 72–96 hours after LPS) and reduced lung vascular injury and extravascular water content induced by LPS. However, blocking with anti-α4 or anti-α5 integrin antibody or shRNA-mediated silencing of α4 or α5 integrins in donor BMPCs failed to prevent the vascular injury or edema formation and mortality. Thus, α4 and α5 integrin-dependent adhesion of BMPCs in lung tissue plays a critical role in preventing lung vascular injury and increasing survival in a mouse model of LPS-induced acute lung injury.
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影响因子：
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