Permeability of filters used for immunoisolation.
Permeability of filters used for immunoisolation.
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用于免疫隔离的过滤器的渗透性。
DOI：
10.1089/ten.1996.2.289
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发表时间：
1996
影响因子：
--
通讯作者：
Yoshito Ikada
中科院分区：
文献类型：
--
作者：
Hiroo Iwata;Noriyuki Morikawa;Yoshito Ikada
将朗格汉斯胰岛(胰岛)包裹在过滤器中进行免疫隔离，使其在植入后与宿主免疫系统隔离，是一种特别吸引人的生物人工胰腺方法。过滤器应该具有良好的半渗透性，这样免疫系统的破坏性成分就不能到达植入的胰岛。此外，氧气和营养物质的供应速度应该足够高，以维持组织的生存能力。在目前的工作中，我们进行了不同分子大小的溶质通过核孔过滤器和XM-50超过滤器的体外扩散研究，这两种过滤器已被优先用于免疫分离。微溶质的高渗透性不会因为任何过滤器的存在而降低太多，这意味着即使在过滤器中封闭，氧气和营养物质也可以通过扩散有效地提供给活细胞。由于同种异体移植排斥反应的主要原因是T淋巴细胞激活细胞免疫，而包括抗体和补体蛋白在内的体液免疫在异种移植排斥反应中起主要作用，因此对滤器半通透性的要求高度依赖于胰岛组织的供体。直径约10微米的T淋巴细胞，由于孔径小于2微米，既不能通过核孔，也不能通过XM-50过滤器。因此，所有的滤器都有望成为同种异体胰岛移植的有效免疫屏障。尽管XM-50超滤器和0.015微米直径的核孔过滤器在压力驱动过程(如超滤)中可以根据大分子的大小(约50kD)大幅分离大分子，但在浓度驱动过程(如扩散)中发现这些过滤器失去了大溶质的分级效率。换句话说，核孔过滤器和XM-50超滤器都不能阻止免疫球蛋白G在扩散过程中通过。这一发现表明，这些过滤器不能保护异种胰岛免受宿主免疫系统的攻击，因为生物大分子可能通过浓度驱动力渗透到这些过滤器中。
Immunoisolation of islets of Langerhans (islets) by their enclosure in a filter to isolate them from the host immune system following implantation is a particularly attractive method for bioartificial pancreas. The filter should have excellent semipermeability so that damaging components of the immune system cannot reach the implanted islets. In addition, oxygen and nutrients should be supplied at a sufficiently high rate to maintain tissue viability. In the present work we conducted in vitro diffusion studies of solutes with various molecular sizes through Nuclepore filters and an XM-50 ultrafilter, which have been preferentially used for immunoisolation. The high permeability of microsolutes was not reduced much by the presence of any filters, implying that oxygen and nutrients could be effectively supplied to living cells by diffusion even if enclosed in a filter. Since the predominant cause of allograft rejection is activation of cellular immunity by T lymphocyte, while humoral immunity including antibodies and complement proteins plays a major role in the rejection of xenografts, requirements for the semipermeability of filters highly depends on the donor of islet tissue. T lymphocytes with a diameter of about 10 microm can permeate through neither Nuclepore nor XM-50 filters because their pore size is less than 2 microm. Therefore all of the filters are anticipated to act as effective immunobarrier for islet allografts. Although the XM-50 ultrafilter and 0.015-microm-diameter Nuclepore filter can sharply fractionate macromolecules in accordance with their size (around 50 kD) in a pressure-driven process such as ultrafiltration, these filters were found to lose the fractionation efficiency of macrosolutes in a concentration-driven process such as diffusion. In other words, neither the Nuclepore filters nor the XM-50 ultrafilter could prevent passage of immunoglobulin G in the diffusion process. This finding suggests that these filters cannot protect xenogeneic islets from the host immune system because biomacromolecules may permeate through these filters by the concentration-driven force.