Sokolov Andrey, Hellerud Bernt Christian, Lambris John D, Johannessen Erik A, Mollnes Tom Eirik
Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway.
J Diabetes Sci Technol. 2011 Nov 1;5(6):1490-8. doi: 10.1177/193229681100500625.
Continuous monitoring of glucose by implantable microfabricated devices offers key advantages over current transcutaneous glucose sensors that limit usability due to their obtrusive nature and risk of infection. A successful sensory implant should be biocompatible and retain long-lasting function. Polymorphonuclear leukocytes (PMN) play a key role in the inflammatory system by releasing enzymes, cytokines, and reactive oxygen species, typically as a response to complement activation. The aim of this study was to perform an in vitro analysis of PMN activation as a marker for biocompatibility of materials and to evaluate the role of complement in the activation of PMN.
Fifteen candidate materials of an implantable glucose sensor were incubated in lepirudin-anticoagulated whole blood. The cluster of differentiation molecule 11b (CD11b) expression on PMN was analyzed with flow cytometry and the myeloperoxidase (MPO) concentration in plasma was analyzed with enzyme-linked immunosorbent assay. Complement activation was prevented by the C3 inhibitor compstatin or the C5 inhibitor eculizumab.
Three of the biomaterials (cellulose ester, polyamide reverse osmosis membrane, and polyamide thin film membrane), all belonging to the membrane group, induced a substantial and significant increase in CD11b expression and MPO release. The changes were virtually identical for these two markers. Inhibition of complement with compstatin or eculizumab reduced the CD11b expression and MPO release dose dependently and in most cases back to baseline. The other 12 materials did not induce significant PMN activation.
Three of the 15 candidate materials triggered PMN activation in a complement-dependent manner and should therefore be avoided for implementation in implantable microsensors.
与目前的经皮葡萄糖传感器相比，通过植入式微制造设备持续监测葡萄糖具有关键优势，经皮葡萄糖传感器因其侵入性和感染风险而限制了其可用性。成功的传感植入物应具有生物相容性并保持持久功能。多形核白细胞（PMN）通过释放酶、细胞因子和活性氧在炎症系统中发挥关键作用，这通常是对补体激活的反应。本研究的目的是对PMN激活进行体外分析，作为材料生物相容性的标志物，并评估补体在PMN激活中的作用。
将15种可植入葡萄糖传感器的候选材料在水蛭素抗凝的全血中孵育。用流式细胞术分析PMN上分化簇分子11b（CD11b）的表达，并用酶联免疫吸附测定法分析血浆中的髓过氧化物酶（MPO）浓度。用C3抑制剂compstatin或C5抑制剂依库珠单抗阻止补体激活。
三种生物材料（纤维素酯、聚酰胺反渗透膜和聚酰胺薄膜）均属于膜组，均诱导CD11b表达和MPO释放显著增加。这两个标志物的变化几乎相同。用compstatin或依库珠单抗抑制补体可剂量依赖性地降低CD11b表达和MPO释放，在大多数情况下可降至基线水平。其他12种材料未诱导明显的PMN激活。
15种候选材料中的三种以补体依赖的方式触发PMN激活，因此应避免在可植入微传感器中使用。
