Diminished adhesion and activation of platelets and neutrophils with CD47 functionalized blood contacting surfaces

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• 作者：Matthew J. Finley^a ; ^b ; Lubica Rauova^b ; ^c ; Ivan S. Alferiev^a ; ^b ; John W. Weisel^b ; ^d ; Robert J. Levy^a ; ^b ; Stanley J. Stachelek^a ; ^b ; ^{stachelek@email.chop.edu}
• 关键词：Blood compatibility ; Biomimetic material ; Surface modification ; Platelet adhesion ; Platelet activation
• 刊名：Biomaterials
• 出版年：2012
• 期刊代码：7_01429612
• 类别：ms
• 出版时间：August, 2012
• 卷：33
• 期：24
• 页码：5803-5811
• 文件大小：566 K

摘要

CD47 is a ubiquitously expressed transmembrane protein that, through signaling mechanisms mediated by signal regulatory protein alpha (SIRP伪1), functions as a biological marker of 鈥榮elf-recognition鈥? We showed previously that inflammatory cell attachment to polymeric surfaces is inhibited by the attachment of biotinylated recombinant CD47 (CD47B). We test herein the hypothesis that CD47 modified blood conduits can reduce platelet and neutrophil activation under clinically relevant conditions. We appended a poly-lysine tag to the C-terminus of recombinant CD47 (CD47L) allowing for covalent linkage聽to the polymer. SIRP伪1 expression was confirmed in isolated platelets. We then compared biocompatibility between CD47B and CD47L functionalized polyvinyl chloride (PVC) surfaces and unmodified control PVC surfaces. Quantitative and Qualitative analysis of blood cell attachment to CD47B and CD47L surfaces, via scanning electron microscopy, showed strikingly fewer platelets attached to CD47 modified surfaces compared to control. Flow cytometry analysis showed that activation markers for neutrophils (CD62L) and platelets (CD62P) exposed to CD47 modified PVC were equivalent to freshly acquired control blood, while significantly elevated in the unmodified PVC tubing. In addition, ethylene oxide gas sterilization did not inhibit the efficacy of the CD47 modification. In conclusion, CD47 modified PVC inhibits both the adhesion and activation of platelets and neutrophils.