Histone H2B as a functionally important plasminogen receptor on macrophages
Histone H2B as a functionally important plasminogen receptor on macrophages
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DOI：
10.1182/blood-2007-03-079392
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发表时间：
2007-11-15
期刊：
影响因子：
20.3
通讯作者：
Plow, Edward F.
中科院分区：
文献类型：
--
作者：
Das, Riku;Burke, Tim;Plow, Edward F.
纤溶酶原（Pig）促进炎性细胞募集，该功能取决于其与Pig受体（Pig-Rs）的结合。然而，对于细胞迁移至关重要的Pig-R并没有很好地定义。评估了三种先前表征的Pig-R（α-烯醇化酶、膜联蛋白2和p11）和最近鉴定的PIg-R（组蛋白H2 B [H2 B]）对巨噬细胞上的Pig结合和功能的贡献。分析了两种小鼠巨噬细胞系（RAW 264.7和J774A.1）和巯基乙酸盐诱导的小鼠腹腔巨噬细胞。所有4个PIg-R都存在于这些细胞的表面上，并且与外周血单核细胞相比，在巯基乙酸盐-included巨噬细胞上显示出增强的表达。使用针对每个PIg-R的阻断Fab片段，H2 B支持约50%的Pig结合能力，而其他Pig-R贡献小于25%。抗-H2 B Fab也证明了这种PIg-R在纤溶酶产生和基质侵袭中的主要作用。当小鼠静脉注射抗-H2 B Fab时，在24、48和72小时，响应巯基乙酸盐的腹膜巨噬细胞募集减少约45%，对血液单核细胞水平没有影响。总之，这些数据表明，多个Pig-R确实有助于Pig与巨噬细胞的结合，其中，H2 B起着非常突出和功能上重要的作用。
Plasminogen (Pig) facilitates inflammatory cell recruitment, a function that depends upon its binding to Pig receptors (Pig-Rs). However, the Pig-Rs that are critical for cell migration are not well defined. Three previously characterized Pig-Rs (a-enolase, annexin 2, and p11) and a recently identified PIg-R (histone H2B [H2B]) were assessed for their contribution to Pig binding and function on macrophages. Two murine macrophage cell lines (RAW 264.7 and J774A.1) and mouse peritoneal macrophages induced by thioglycollate were analyzed. All 4 PIg-Rs were present on the surface of these cells and showed enhanced expression on the thioglycollate-incluced macrophages compared with peripheral blood monocytes. Using blocking Fab fragments to each PIg-R, H2B supported approximately 50% of the Pig binding capacity, whereas the other Pig-Rs contributed less than 25%. Anti-H2B Fab also demonstrated a major role of this PIg-R in plasmin generation and matrix invasion. When mice were treated intravenously with anti-H2B Fab, perlitoneal macrophage recruitment in response to thioglycollate was reduced by approximately 45% at 24, 48, and 72 hours, with no effect on blood monocyte levels. Taken together, these data suggest that multiple Pig-Rs do contribute to Pig binding to macrophages, and among these, H2B plays a very prominent and functionally important role.