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PHAGOCYTE-SURFACE INTERACTIONS

吞噬细胞表面相互作用

基本信息

批准号：
2460102
负责人：
JOHN W EATON
金额：
$ 19.4万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-08-01 至 2000-07-31
项目状态：
已结题

项目摘要

DESCRIPTION: These investigations are aimed at determining the mechanisms responsible for the inflammatory and fibrotic changes often triggered by implanted biomaterials. Although implanted medical devices represent an increasingly important therapeutic modality, little is known of the determinants of biocompatibility. The acute and chronic inflammatory responses to implants involving the early phagocyte recruitment to the implant surface often followed by fibrosis are puzzling in view of the generally inert and non-toxic nature of most implantable materials. The Applicants have recently found that the surface adsorption of fibrin(ogen) is a necessary precedent to the attraction of both macrophages and neutrophils to the surfaces of polymeric implants and, probably to later fibrotic changes. Although the requirement for surface fibrinogen adsorption is now established, the secondary events (e.g., possible modifications of bound fibrin(ogen), possible binding of ancillary proteins which may amplify fibrinogen- dependent inflammatory responses, mechanisms of phagocyte recruitment, binding and activation, and processes responsible for the ultimate occurrence of fibrotic changes remain unclear. Therefore, the first aim of the proposed work is that of identifying novel epitopes of fibrin(ogen) which may appear following the surface adsorption and probably conformational change of this complex protein. They shall then attempt to determine the mechanisms involved in phagocyte adhesion to protein-coated implant surfaces, as well as the effects of such cell: protein:surface interactions on the metabolic and pro-inflammatory activities of adherent phagocytes. Finally, preliminary studies will be carried out on the importance of the primary protein adsorption and early wave of phagocyte accumulation on subsequent implant associated fibrotic changes. It is hoped that a better knowledge of these complex host: implant interactions may improve our present understanding of what constitutes biocompatibility and lead to improvements in the design of biomaterial surfaces.

描述：这些调查旨在确定导致炎症和纤维化变化的机制通常由植入的生物材料引发虽然植入的医疗器械代表一种越来越重要的治疗方式，已知的生物相容性的决定因素。急性和慢性早期吞噬细胞对植入物的炎症反应在植入物表面的募集通常随后是纤维化，考虑到大多数化合物的通常惰性和无毒性质，可植入材料申请人最近发现，纤维蛋白（原）的表面吸附是巨噬细胞和中性粒细胞的吸引力，聚合物植入物，可能导致后来的纤维化变化。虽然现在建立了表面纤维蛋白原吸附的要求，次要事件（例如，结合纤维蛋白（原）的可能修饰，可能结合辅助蛋白，其可放大纤维蛋白原- 依赖性炎症反应，吞噬细胞募集机制，绑定和激活，以及负责最终纤维化变化的发生仍不清楚。因此，第一个目标这项工作的主要目的是鉴定纤维蛋白（原），其可能在表面吸附后出现，可能是这个复杂蛋白质的构象变化。然后，试图确定吞噬细胞粘附到蛋白质包被的植入物表面，以及这种细胞的作用：蛋白质：代谢和促炎的表面相互作用粘附吞噬细胞的活性。最后，初步研究将对初级蛋白吸附的重要性进行了研究，随后植入物上的吞噬细胞积聚波相关纤维化变化希望能更好地了解这些复杂的主机：植入物的相互作用可能会改善我们目前对构成生物相容性，并导致设计的改进，生物材料表面。