Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages.
Vitronectin inhibits efferocytosis through interactions with apoptotic cells as well as with macrophages.
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玻染蛋白通过与凋亡细胞以及巨噬细胞的相互作用来抑制胚细胞增多症。
DOI：
10.4049/jimmunol.1200625
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发表时间：
2013-03-01
期刊：
影响因子：
--
通讯作者：
Zmijewski JW
中科院分区：
文献类型：
--
作者：
Bae HB;Tadie JM;Jiang S;Park DW;Bell CP;Thompson LC;Peterson CB;Thannickal VJ;Abraham E;Zmijewski JW
有效清除凋亡细胞，特别是凋亡中性粒细胞，是成功解决急性炎症条件的必要条件。在本实验中，我们发现，虽然玻璃连接蛋白和整合素的相互作用降低了巨噬细胞摄取凋亡细胞的能力，但玻璃连接蛋白与凋亡细胞表面尿激酶型纤溶酶原激活剂受体（uPAR）的相互作用对efferocytosis也有同样重要的抑制作用。玻璃体粘连蛋白与纤溶酶原激活物抑制剂-1 （PAI-1）预先孵育可消除其抑制凋亡细胞吞噬的能力。同样，用可溶性uPAR或uPAR抗体孵育凋亡细胞可显著减少胞浆增多。在lps诱导的ALI环境下，与野生型（vtn+/+）小鼠相比，玻璃体连接蛋白缺乏（vtn−/−）小鼠的支气管肺泡灌洗液中发现efferocytosis增强和中性粒细胞数量减少。此外，与引入vtn−/−小鼠肺后的vtn+/+中性粒细胞相比，凋亡的vtn−/−的清除率增加。在气管内灌注前，用纯化的玻璃体粘连蛋白孵育凋亡的vn−/−中性粒细胞可减少体内的efferocytic。这些发现表明，玻璃体连接蛋白对efferocytosis的抑制作用涉及与吞噬吞噬细胞和凋亡靶细胞的相互作用。
Effective removal of apoptotic cells, particularly apoptotic neutrophils, is essential for the successful resolution of acute inflammatory conditions. In the present experiments, we found that whereas interaction between vitronectin and integrins diminished the ability of macrophages to ingest apoptotic cells, interaction between vitronectin with urokinase type Plasminogen Activator receptor (uPAR) on the surface of apoptotic cells also had equally important inhibitory effects on efferocytosis. Pre-incubation of vitronectin with Plasminogen Activator inhibitor-1 (PAI-1) eliminated its ability to inhibit phagocytosis of apoptotic cells. Similar, incubation of apoptotic cells with soluble uPAR or antibodies to uPAR significantly diminished efferocytosis. In the setting of LPS-induced ALI, enhanced efferocytosis and decreased numbers of neutrophils was found in bronchoalveolar lavage obtained from vitronectin deficient (vtn−/−) mice compared to wild type (vtn+/+) mice. Furthermore, there was increased clearance of apoptotic vtn−/− as compared to vtn+/+ neutrophils after introduction into the lungs of vtn−/− mice. Incubation of apoptotic vtn−/− neutrophils with purified vitronectin prior to intratracheal instillation decreased efferocytosis in vivo. These findings demonstrate that the inhibitory effects of vitronectin on efferocytosis involve interactions with both the engulfing phagocyte as well as the apoptotic target cell.
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影响因子：
3.3
作者：
Foster, WM;Walters, DM;Miller, LM
通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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作者：
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DOI：
10.1073/pnas.0609661104
发表时间：
2007-03-20
影响因子：
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作者：
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影响因子：
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