Circulating complexes of the vitamin D binding protein with G-actin induce lung inflammation by targeting endothelial cells.
Circulating complexes of the vitamin D binding protein with G-actin induce lung inflammation by targeting endothelial cells.
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维生素D结合蛋白与G-肌动蛋白的循环复合物通过靶向内皮细胞诱导肺部炎症。
DOI：
10.1016/j.imbio.2013.10.001
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发表时间：
2014-03
期刊：
影响因子：
2.8
通讯作者：
Kew, Richard R.
中科院分区：
文献类型：
--
作者：
Ge, Lingyin;Trujillo, Glenda;Miller, Edmund J.;Kew, Richard R.
本研究利用DBP缺失（- / -）小鼠研究了维生素D结合蛋白（DBP）在体内的肌动蛋白清除功能。在野生型（DBP+/+）和DBP - / -小鼠中静脉注射g -肌动蛋白，与预期相反，DBP+/+小鼠出现了更严重的急性肺部炎症。炎症局限于肺部，注射后1.5小时和4小时病理改变明显，但24小时基本消退。DBP+/+肺组织学显示明显更多的血管渗漏、出血和肺泡壁增厚。流式细胞术分析全肺匀浆显示，在1.5和4小时时，DBP+/+小鼠肺中中性粒细胞的浸润明显增加。注射肌动蛋白4小时后，DBP+/+小鼠支气管肺泡灌洗液中蛋白质和白细胞的数量也有所增加。纯化的DBP-actin复合物在体外对培养的人肺微血管内皮细胞（HLMVEC）和人脐静脉内皮细胞（HUVEC）没有激活补体或中性粒细胞的作用，但可引起损伤和死亡。用dbp -肌动蛋白处理的细胞在4小时后活性显著降低，如果细胞在新鲜培养基中再培养24小时，这种影响是可逆的。然而，24小时DBP-actin复合物治疗显示细胞死亡显著增加（HLMVEC为95%，HUVEC为45%）。内皮细胞死亡的机制通过caspase-3依赖性（HUVEC）和非依赖性（HLMVEC）两种途径。这些结果表明，dbp -肌动蛋白复合物水平升高和/或长时间暴露可诱导内皮细胞损伤和死亡，特别是在肺微血管中。
This study investigated the actin scavenger function of the vitamin D binding protein (DBP) in vivo using DBP null (−/−) mice. Intravenous injection of G-actin into wild-type (DBP+/+) and DBP−/− mice showed that contrary to expectations, DBP+/+ mice developed more severe acute lung inflammation. Inflammation was restricted to the lung and pathological changes were clearly evident at 1.5 and 4 hours post-injection but were largely resolved by 24 hours. Histology of DBP+/+ lungs revealed noticeably more vascular leakage, hemorrhage and thickening of the alveolar wall. Flow cytometry analysis of whole lung homogenates showed significantly increased neutrophil infiltration into DBP+/+ mouse lungs at 1.5 and 4 hours. Increased amounts of protein and leukocytes were also noted in bronchoalveolar lavage fluid from DBP+/+ mice 4 hours after actin injection. In vitro, purified DBP-actin complexes did not activate complement or neutrophils but induced injury and death of cultured human lung microvascular endothelial cells (HLMVEC) and human umbilical vein endothelial cells (HUVEC). Cells treated with DBP-actin showed a significant reduction in viability at 4 hours, this effect was reversible if cells were cultured in fresh media for another 24 hours. However, a 24-hour treatment with DBP-actin complexes showed a significant increase in cell death (95% for HLMVEC, 45% for HUVEC). The mechanism of endothelial cell death was via both caspase-3 dependent (HUVEC) and independent (HLMVEC) pathways. These results demonstrate that elevated levels and/or prolonged exposure to DBP-actin complexes may induce endothelial cell injury and death, particularly in the lung microvasculature.
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影响因子：
8.8
作者：
Dahl, P;Schiodt, FV;Tygstrup, N
通讯作者：
Tygstrup, N
影响因子：
15.9
作者：
HARPER, KD;MCLEOD, JF;HADDAD, JG
通讯作者：
HADDAD, JG
DOI：
10.1073/pnas.241516998
发表时间：
2001-11-20
影响因子：
11.1
作者：
Nykjaer, A;Fyfe, JC;Christensen, EI
通讯作者：
Christensen, EI
影响因子：
3.1
作者：
Dahl, B;Schiodt, FV;Lee, WM
通讯作者：
Lee, WM
白细胞运动和趋化性。评估的新方法，并证明了细胞衍生的趋化因子。
影响因子：
15.3
作者：
Zigmond, S H;Hirsch, J G
通讯作者：
Hirsch, J G