Diekjiirgen Dorina, Astashkina Anna, Grainger David W, Holt Dolly, Brooks Amanda E
a Department of Pharmaceutics and Pharmaceutical Chemistry , 20 South 2030 East BPRB Room 190B, University of Utah , Salt Lake City , UT , 84112-5820 , USA.
J Biomater Sci Polym Ed. 2012;23(9):1231-54. doi: 10.1163/092050611X580382. Epub 2012 May 8.
Recent efforts show that significantly reducing implant-adsorbed proteins does not avoid the foreign body response. Fluorinated surfaces are commonly used to passivate cell-mediated inflammatory responses to implanted materials but adsorb host proteins and facilitate the attachment and proliferation of macrophages. This study considers in vitro macrophage activation to fluorinated TeflonAF(®) compared to tissue-culture polystyrene using pre-adsorbed proteins (fibrinogen, BSA, collagen and elastin). Primary macrophage cultures adhere on all pre-adsorbed protein surfaces in a protein concentration-dependent manner and activate to the same extent after 72 h, regardless of surface chemistry. However, macrophages alter their cultured adherent morphology depending on which protein is pre-adsorbed to these surfaces. Macrophages cultured on TeflonAF(®) on all pre-adsorbed proteins produced overall higher levels of the pro-inflammatory cytokines - TNF-α, IL-6, IL-1β or MCP-1 - than those cultured on tissue-culture polystyrene and those cultured in serum-free media. However, at 72 h, macrophages adherent on BSA or fibrinogen pre-adsorbed surfaces failed to exhibit increased amounts of TNF-a, IL-6 or IL-1/S on either TeflonAF(®) or TCPS, as well as MCP-1 on TCPS, in the presence of activating lipopolysaccharide. Different cell responses to pre-adsorbed proteins reflect substrate-specific regulation of macrophage cytokine secretion, indicative of LPS tolerance distinct from secondary macrophage cultures, and also distinct from macrophages adherent to surfaces in the absence of proteins. This result has bearing on connecting macrophage adhesion via adsorbed proteins on (fluorinated) biomaterials, and their resulting chronic activation that yields the FBR and possibly reduces effective macrophage clearance of microbes around implanted materials.
最近的研究表明，大幅减少植入物吸附的蛋白质并不能避免异物反应。氟化表面通常用于钝化细胞介导的对植入材料的炎症反应，但会吸附宿主蛋白质并促进巨噬细胞的附着和增殖。本研究比较了预吸附蛋白质（纤维蛋白原、牛血清白蛋白、胶原蛋白和弹性蛋白）的氟化聚四氟乙烯AF（®）与组织培养聚苯乙烯对巨噬细胞的体外激活作用。原代巨噬细胞培养物以蛋白质浓度依赖的方式附着在所有预吸附蛋白质表面，并且在72小时后无论表面化学性质如何都能激活到相同程度。然而，巨噬细胞会根据预吸附在这些表面上的蛋白质改变其培养的附着形态。在所有预吸附蛋白质的聚四氟乙烯AF（®）上培养的巨噬细胞产生的促炎细胞因子——肿瘤坏死因子-α、白细胞介素-6、白细胞介素-1β或单核细胞趋化蛋白-1——总体水平高于在组织培养聚苯乙烯上培养的巨噬细胞以及在无血清培养基中培养的巨噬细胞。然而，在72小时时，在存在激活脂多糖的情况下，附着在预吸附牛血清白蛋白或纤维蛋白原表面的巨噬细胞在聚四氟乙烯AF（®）或组织培养聚苯乙烯上均未表现出肿瘤坏死因子-α、白细胞介素-6或白细胞介素-1β水平增加，在组织培养聚苯乙烯上也未表现出单核细胞趋化蛋白-1水平增加。对预吸附蛋白质的不同细胞反应反映了巨噬细胞细胞因子分泌的底物特异性调节，这表明脂多糖耐受性不同于二级巨噬细胞培养物，也不同于在无蛋白质情况下附着在表面的巨噬细胞。这一结果对于通过（氟化）生物材料上吸附的蛋白质连接巨噬细胞黏附以及由此产生的慢性激活具有重要意义，这种慢性激活会导致异物反应，并可能降低巨噬细胞对植入材料周围微生物的有效清除。
