The effect of CD47 modified polymer surfaces on inflammatory cell attachment and activation.

The effect of CD47 modified polymer surfaces on inflammatory cell attachment and activation.
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DOI:
10.1016/j.biomaterials.2011.02.053
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发表时间:
2011-07
期刊:
影响因子:
14
通讯作者:
Levy, Robert J.
Levy, Robert J.
中科院分区:
工程技术1区
文献类型:
--
作者:
Stachelek, Stanley J.;Finley, Matthew J.;Alferiev, Ivan S.;Wang, Fengxiang;Tsai, Richard K.;Eckells, Edward C.;Tomczyk, Nancy;Connolly, Jeanne M.;Discher, Dennis E.;Eckmann, David M.;Levy, Robert J.

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CD 47是一种跨膜蛋白,是“自我”的标志物。CD 47与其在白细胞和巨噬细胞中的同源受体信号调节蛋白α(SIRPα)结合,可抑制炎性细胞附着。我们假设重组CD 47在聚合物表面上的固定会减少炎症。通过光活化化学将重组CD 47附加到聚氯乙烯(PVC)或聚氨酯(PU)表面。细胞培养研究表明,CD 47固定化显著减少人中性粒细胞(HL-60)和人单核细胞衍生的巨噬细胞(MDM)(THP-1)分别与PVC和PU的附着。抗SIRPα的中和抗体可抑制THP-1和HL-60与PU和PVC表面的结合。该抗体还增加了SIRPα酪氨酸磷酸化水平,从而表明SIRPα介导的信号传导在预防炎性细胞附着中的直接作用。在离体流动回路中使用人血的研究表明,与未改性管或聚-2-甲氧基-丙烯酸乙酯(PMEA)涂层管相比,CD 47改性PVC管显著降低了细胞结合和中性粒细胞活化。在10周大鼠皮下植入物中,与未改性PU相比,CD 47官能化PU膜显示MDM介导的氧化降解标记物显著减少。总之,CD 47功能化表面可以抵抗体外和体内的炎性细胞相互作用。
CD47 is a transmembrane protein that is a marker of “self”. CD47 binding to its cognate receptor in leukocytes and macrophages, signal regulatory protein alpha (SIRPα), causes inhibition of inflammatory cell attachment. We hypothesized that immobilization of recombinant CD47 on polymeric surfaces would reduce inflammation. Recombinant CD47 was appended to polyvinyl chloride (PVC) or polyurethane (PU) surfaces via photoactivation chemistry. Cell culture studies showed that CD47 immobilization significantly reduced human neutrophil (HL-60) and human monocyte derived macrophage (MDM) (THP-1) attachment to PVC and PU respectively. A neutralizing antibody, directed against SIRPα, inhibited THP-1 and HL-60 binding to PU and PVC surfaces respectively. This antibody also increased the level of SIRPα tyrosine phosphorylation, thereby indicating a direct role for SIRPα mediated signaling in preventing inflammatory cell attachment. Studies using human blood in an ex vivo flow-loop showed that CD47 modified PVC tubing significantly reduced cell binding and neutrophil activation compared to unmodified tubing or poly-2-methoxy-ethylacrylate (PMEA) coated tubing. In ten-week rat subdermal implants, CD47 functionalized PU films showed a significant reduction in markers of MDM mediated oxidative degradation compared to unmodified PU. In conclusion, CD47 functionalized surfaces can resist inflammatory cell interactions both in vitro and in vivo.
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