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A central role for plasminogen in the inflammatory response to biomaterials
Author(s) -
Busuttil S. J.,
Ploplis V. A.,
Castellino F. J.,
Tang L.,
Eaton J. W.,
Plow E. F.
Publication year - 2004
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2004.00916.x
Subject(s) - plasmin , monocyte , peritoneum , macrophage , aprotinin , chemistry , cell adhesion , inflammation , immunology , adhesion , pharmacology , medicine , in vitro , pathology , biochemistry , organic chemistry , enzyme
Summary. 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.