Department of Pathology and Laboratory Medicine, University of Pennsylvania, 422 Curie Blvd., Philadelphia, PA 19104, USA.
FASEB J. 2013 Jul;27(7):2768-76. doi: 10.1096/fj.12-225888. Epub 2013 Apr 4.
Although complement is a known contributor to biomaterial-induced complications, pathological implications and therapeutic options remain to be explored. Here we investigated the involvement of complement in the inflammatory response to polypropylene meshes commonly used for hernia repair. In vitro assays revealed deposition of complement activation fragments on the mesh after incubation in plasma. Moreover, significant mesh-induced complement and granulocyte activation was observed in plasma and leukocyte preparations, respectively. Pretreatment of plasma with the complement inhibitor compstatin reduced opsonization >2-fold, and compstatin and a C5a receptor antagonist (C5aRa) impaired granulocyte activation by 50 and 67%, respectively. We established a clinically relevant mouse model of implantation and could confirm deposition of C3 activation fragments on mesh implants in vivo using immunofluorescence. In meshes extracted after subcutaneous or peritoneal implantation, the amount of immune cell infiltrate in mice deficient in key complement components (C3, C5aR), or treated with C5aRa, was approximately half of that observed in wild-type littermates or mice treated with inactive C5aRa, respectively. Our data suggest that implantation of a widely used surgical mesh triggers the formation of an inflammatory cell microenvironment at the implant site through complement activation, and indicates a path for the therapeutic modulation of implant-related complications.
虽然补体是导致生物材料诱导并发症的已知因素，但病理影响和治疗选择仍有待探索。在这里，我们研究了补体在用于疝修补的常见聚丙烯网片引起的炎症反应中的作用。体外实验显示，在等离子体中孵育后，补体激活片段沉积在网片上。此外，在血浆和白细胞制剂中分别观察到显著的网片诱导的补体和粒细胞激活。用补体抑制剂 compstatin 预处理血浆可使调理作用降低 >2 倍，compstatin 和 C5a 受体拮抗剂（C5aRa）分别使粒细胞激活降低 50%和 67%。我们建立了一种具有临床相关性的植入物小鼠模型，并用免疫荧光法在体内证实了 C3 激活片段在网片植入物上的沉积。在皮下或腹膜内植入的网片中，缺乏关键补体成分（C3、C5aR）的小鼠或用 C5aRa 治疗的小鼠中，免疫细胞浸润的数量分别约为野生型同窝仔鼠或用无活性 C5aRa 治疗的小鼠的一半。我们的数据表明，广泛使用的外科网片的植入通过补体激活在植入部位触发炎症细胞微环境的形成，并为治疗调节与植入物相关的并发症提供了途径。
