Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II
Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II
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DOI：
10.1182/blood.v97.3.777
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发表时间：
2001-02-01
期刊：
影响因子：
20.3
通讯作者：
Hajjar, KA
中科院分区：
文献类型：
--
作者：
Falcone, DJ;Borth, W;Hajjar, KA
遗传证据证明了纤溶酶原活化在巨噬细胞迁移到损伤和炎症部位、它们去除坏死碎片和它们清除纤维蛋白中的重要性。这些研究鉴定了巨噬细胞表面上的纤溶酶原结合蛋白膜联蛋白II，并确定了其在它们降解和迁移通过细胞外基质的能力中的作用，使用流式细胞术和EGTA洗脱液的Western印迹分析显示膜联蛋白II与RAW 264.7巨噬细胞的钙依赖性结合。配体印迹证明膜联蛋白II与来自RAW 264.7巨噬细胞的结合纤溶酶原的裂解物和膜中的几种蛋白质之一共迁移。RAW264.7巨噬细胞与单克隆抗膜联蛋白II IgG预孵育可抑制（35%）它们与I-125-Lys-纤溶酶原的结合。同样，当细胞与抗膜联蛋白II IgG预孵育时，纤溶酶与人单核细胞衍生的巨噬细胞和THP-1单核细胞的结合被抑制（分别为50%和35%）。在RAW 264.7巨噬细胞上，纤溶酶原与膜联蛋白II结合的抑制显著损害了它们激活纤溶酶原和降解[H-3]的能力。葡糖胺标记的细胞外基质。当膜被细胞外基质包被时，响应单核细胞趋化蛋白-1的THP-1单核细胞通过多孔膜的迁移被阻断。将纤溶酶原添加到单核细胞中恢复了它们通过基质包被的膜的迁移能力，用抗膜联蛋白II IgG预孵育THP-1单核细胞抑制了（60%）它们通过细胞外基质的纤溶酶原依赖性趋化性。这些研究鉴定了膜联蛋白II作为巨噬细胞上的纤溶酶原结合位点，并表明膜联蛋白II在其侵袭性和降解表型中的重要作用。(C)2001年，美国血液学会。
Genetic evidence demonstrates the importance of plasminogen activation in the migration of macrophages to sites of injury and inflammation, their removal of necrotic debris, and their clearance of fibrin, These studies identified the plasminogen binding protein annexin II on the surface of macrophages and determined its role in their ability to degrade and migrate through extracellular matrices, Calcium-dependent binding of annexin II to RAW264.7 macrophages was shown using flow cytometry and Western blot analysis of EGTA eluates, Ligand blots demonstrated that annexin II comigrates with one of several proteins in lysates and membranes derived from RAW264.7 macrophages that bind plasminogen. Preincubation of RAW264.7 macrophages with monoclonal anti-annexin II IgG inhibited (35%) their binding of I-125-Lys-plasminogen, Likewise, plasmin binding to human monocyte-derived macrophages and THP-I monocytes was inhibited (50% and 35%, respectively) when cells were preincubated with anti-annexin II IgG. Inhibition of plasminogen binding to annexin II on RAW264.7 macrophages significantly impaired their ability to activate plasminogen and degrade [H-3]. glucosamine-labeled extracellular matrices, The migration of THP-1 monocytes through a porous membrane, in response to monocyte chemotactic protein-1, was blocked when the membranes were coated with extracellular matrix. The addition of plasminogen to the monocytes restored their ability to migrate through the matrix-coated membrane, Preincubation of THP-1 monocytes with anti-annexin II IgG inhibited (60%) their plasminogen-dependent chemotaxis through the extracellular matrix, These studies identify annexin II as a plasminogen binding site on macrophages and indicate an important role for annexin II in their invasive and degradative phenotype. (C) 2001 by The American Society of Hematology.