A central role for plasminogen in the inflammatory response to biomaterials
A central role for plasminogen in the inflammatory response to biomaterials
复制标题
DOI：
10.1111/j.1538-7836.2004.00916.x
复制
发表时间：
2004-10-01
影响因子：
10.4
通讯作者：
Plow, EF
中科院分区：
文献类型：
--
作者：
Busuttil, SJ;Ploplis, VA;Plow, EF
植入生物材料的炎症反应严重限制了其在患者中的应用。纤溶酶原已被证明在细胞迁移中起核心作用，因此可以调节这种炎症反应。我们试图确定纤溶酶原是否影响植入纤溶酶原缺乏（Plg(-/-)）小鼠的生物材料中炎症细胞的募集。小圆盘聚对苯二甲酸乙二醇酯（一种用于血管移植的材料）通过手术植入野生型和Plg（-/-）小鼠的腹膜。中性粒细胞和单核/巨噬细胞向腹膜和椎间盘的募集情况主要在18小时进行测量。与野生型小鼠相比，Plg（-/-）小鼠的单核/巨噬细胞募集明显减弱。出乎意料的是，Plg-/-小鼠的中性粒细胞募集也明显减少。虽然白细胞向腹膜的募集依赖于纤溶酶原，但迁移细胞对植入物的粘附不是。相比之下，纤维蛋白原缺乏小鼠的粘连减少，但招募没有减少。静脉或腹腔注射纤溶酶原重建Plg（-/-）小鼠单核/巨噬细胞和中性粒细胞募集的差异氨甲环酸（一种纤溶酶原赖氨酸结合位点的抑制剂）在野生型小鼠中抑制白细胞募集，而纤溶酶原抑制剂抑肽蛋白则没有作用。纤溶酶原对植入生物材料的中性粒细胞和单核细胞/巨噬细胞募集均有显著影响。纤溶酶原的作用不同于纤维蛋白原，两种炎症细胞以不同的方式使用纤溶酶原。纤溶酶原是控制植入材料炎症反应的治疗靶点。
The inflammatory response to implanted biomaterials severely limits their deployment in patients. Plasminogen has been shown to play a central role in cell migration, and therefore could regulate this inflammatory response. We sought to determine if plasminogen influences recruitment of inflammatory cells to a biomaterial implanted into plasminogen-deficient (Plg(-/-)) mice. Small disks of polyethylene terephthalate, a material used in vascular grafts, were surgically implanted into the peritoneum of wild-type and Plg(-/-) mice. Recruitment of neutrophils and monocytes/macrophages into the peritoneum and onto the disks was measured, primarily at 18 h. Monocyte/macrophage recruitment was markedly blunted in Plg(-/-) mice compared with wild-type mice. Unexpectedly, neutrophil recruitment was also markedly decreased in the Plg-/- mice. While recruitment of leukocytes into the peritoneum was plasminogen-dependent, the adhesion of the emigrating cells to the implants was not. In contrast, adhesion but not recruitment was reduced in fibrinogen-deficient mice. Reconstitution of Plg(-/-) mice with intravenous or intraperitoneal plasminogen differentially restored monocyte/macrophage and neutrophil recruitment. Tranexamic acid, an inhibitor of the lysine binding sites of plasminogen, suppressed leukocyte recruitment in wild-type mice, but aprotinin, a plasmin inhibitor, did not. Plasminogen exerts a marked influence on both neutrophil and monocyte/macrophage recruitment to implanted biomaterials. This role is distinct from that of fibrinogen, and the two inflammatory cell types use plasminogen in different ways. Plasminogen represents a therapeutic target for controlling the inflammatory response to implanted materials.