Rouhani Foad J, Dor Frank J M F, Cooper David K C
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
Transfusion. 2004 Jul;44(7):1004-12. doi: 10.1111/j.1537-2995.2004.04002.x.
Pigs are a potential source of red blood cells (RBCs) for transfusion into humans, but the presence of galactose-alpha1,3-galactose (Gal) epitopes on their surface, against which humans have anti-Gal, has been perceived as a major barrier. alpha1,3-Galactosyltransferase gene-knockout pigs, which do not express Gal epitopes on RBCs (Gal-/-), have recently become available.
In vitro, RBCs from Gal-/- pigs were exposed to sera from naïve humans or baboons or from baboons previously sensitized to pig antigens; immunoglobulin binding was measured by flow cytometry, and cytotoxicity, by a hemolytic assay. In vivo, relatively small numbers of Gal-/- RBCs were transfused into two nonsensitized untreated baboons. The survival of pig RBCs was detected by flow cytometry.
In vitro, binding of immunoglobulin (Ig) M from naïve human or baboon sera was detected to Gal-/- RBCs but was significantly less than to Gal+/+ RBCs; IgG binding to Gal-/- RBCs was absent or minimal. Sera had minimal cytotoxicity to Gal-/- RBCs compared to Gal+/+ RBCs. Sensitized baboon sera demonstrated much higher IgG binding to Gal-/- RBCs and increased cytotoxicity, but again these were less than to Gal+/+ RBCs. In vivo, the transfusion of relatively small volumes of Gal-/- RBCs was followed by detection of the cells in the baboon's blood for only 5 minutes.
Pig RBCs are rapidly phagocytosed from the primate circulation by a mechanism not involving anti-Gal.
猪是向人类输血的红细胞（RBC）的潜在来源，但猪红细胞表面存在半乳糖-α1,3-半乳糖（Gal）表位，而人类体内存在抗Gal抗体，这被视为一个主要障碍。最近已培育出α1,3-半乳糖基转移酶基因敲除猪，其红细胞上不表达Gal表位（Gal-/-）。
在体外，将Gal-/-猪的红细胞暴露于未接触过猪抗原的人类或狒狒血清中，或暴露于先前已对猪抗原致敏的狒狒血清中；通过流式细胞术检测免疫球蛋白结合情况，通过溶血试验检测细胞毒性。在体内，将相对少量的Gal-/-红细胞输注到两只未致敏且未接受过治疗的狒狒体内。通过流式细胞术检测猪红细胞的存活情况。
在体外，未接触过猪抗原的人类或狒狒血清中的免疫球蛋白（Ig）M可与Gal-/-红细胞结合，但明显少于与Gal+/+红细胞的结合；未检测到或仅有极少的IgG与Gal-/-红细胞结合。与Gal+/+红细胞相比，血清对Gal-/-红细胞的细胞毒性极小。致敏狒狒血清显示出与Gal-/-红细胞有更高的IgG结合以及增加的细胞毒性，但同样低于与Gal+/+红细胞的结合。在体内，输注相对少量的Gal-/-红细胞后，仅在5分钟内在狒狒血液中检测到了这些细胞。
猪红细胞通过一种不涉及抗Gal的机制从灵长类动物循环中迅速被吞噬。
