Immune recognition of exposed xenoantigens on the surface of PEGylated bovine red blood cells.
Immune recognition of exposed xenoantigens on the surface of PEGylated bovine red blood cells.
复制标题
聚乙二醇化牛红细胞表面暴露的异种抗原的免疫识别。
DOI：
10.1002/bit.21908
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发表时间：
2008
影响因子：
3.8
通讯作者：
Palmer,AndreF
中科院分区：
文献类型：
--
作者：
Gundersen,SharonI;Kennedy,MelanieS;Palmer,AndreF
由于输血过程中可能发生的潜在问题和日益严重的血液短缺，我们的团队设计了甲氧基聚乙二醇结合牛红细胞（mPEG-bRBC）作为潜在的通用氧治疗剂。目前的工作研究了与人血浆（hP）孵育的mPEG-bRBC的免疫学特性，并将这些特性与暴露的Galα（1，3）Gal异种抗原相关联。将mPEG-bRBC与hP孵育后，通过流式细胞术评估结合的IgG和IgM的量。流式细胞术还评估了与暴露的Galα（1，3）Gal异种抗原结合的GS-IB 4的量。本研究的结果表明，无论mPEG表面覆盖程度或供体血型如何，大多数hP样本均强烈促进mPEG-bRBC的凝集。来自hP的IgG和IgM与mPEG-bRBC强烈结合。一般而言，Galα（1，3）Gal异种抗原在所有PEG表面覆盖水平下均保持暴露。PEG化确实阻断了一些异种抗原，因为暴露的Galα（1，3）Gal的量随着mPEG表面覆盖度的增加而减少。然而，这不足以防止强烈的凝集反应。总而言之，本研究的结果表明，目前的bRBC聚乙二醇化策略对于免疫沉默氧疗法的开发并不令人满意。Biotechnol. Bioeng. 2008;101：337-344.© 2008 Wiley Periodicals，Inc.
Due to potential problems that can occur during blood transfusion and increasing blood shortages, our group engineered methoxypolyethylene glycol conjugated bovine red blood cells (mPEG‐bRBCs) as a potential universal oxygen therapeutic. This current work investigates the immunological properties of mPEG‐bRBCs incubated with human plasma (hP) and correlates these properties to exposed Galα(1,3)Gal xenoantigens. After mPEG‐bRBCs were incubated with hP, the amount of bound IgG and IgM was assessed via flow cytometry. Flow cytometry also assessed the amount of GS‐IB4 bound to exposed Galα(1,3)Gal xenoantigens. The results of this study demonstrate that most hP samples strongly promote agglutination of mPEG‐bRBCs regardless of the extent of mPEG surface coverage or donor blood type. IgG and IgM from hP bound strongly to mPEG‐bRBCs. In general, the Galα(1,3)Gal xenoantigen remains exposed at all levels of PEG surface coverage. PEGylation did block some of the xenoantigens as the amount of exposed Galα (1,3)Gal decreased with increased mPEG surface coverage. However, this was not sufficient to prevent a strong agglutination reaction. Taken together, the results of this study indicate that the current strategy for PEGylating bRBCs is unsatisfactory for the development of immunologically silent oxygen therapeutics. Biotechnol. Bioeng. 2008;101: 337–344. © 2008 Wiley Periodicals, Inc.