Antibody- and complement-independent phagocytotic and cytolytic activities of human macrophages toward porcine cells
Antibody- and complement-independent phagocytotic and cytolytic activities of human macrophages toward porcine cells
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DOI：
10.1111/j.1399-3089.2005.00222.x
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发表时间：
2005-05-01
影响因子：
3.9
通讯作者：
Asahara, T
中科院分区：
文献类型：
--
作者：
Ide, K;Ohdan, H;Asahara, T
背景：已推测宿主巨噬细胞有助于移植异种细胞的快速清除。为了解决这种可能性，在没有抗体和补体因子的情况下，体外测定了人巨噬细胞对异种猪细胞的吞噬和杀细胞活性。方法：分别从志愿者外周血和移植肝灌流液中获取人外周血单核细胞来源的巨噬细胞(P-巨噬细胞)和网状内皮巨噬细胞(RE-巨噬细胞)。将5-(和6-)羧基荧光素二乙酸酯琥珀酰亚胺酯(CFSE)标记的人自体红细胞(Auto-RBC)、ABO血型不合的RBC(Incom-RBC)和异种猪RBC(Xeno-RbCs)与人巨噬细胞孵育，通过流式细胞仪和共聚焦显微镜鉴定吞噬RBC的巨噬细胞为CFSE阳性细胞。结果：人RE-巨噬细胞能自发吞噬异种红细胞，对异种红细胞有明显的杀伤活性，但对自体红细胞和内源性红细胞无明显杀伤作用。异种红细胞表面α-半乳糖异种抗原(α-Gal)表位的消除并不能阻止RE-巨噬细胞的吞噬和杀细胞活性。结论：这些发现表明人巨噬细胞对猪细胞的吞噬和杀细胞活性是由非α-Gal的因素启动的，其机制与抗体/补体调理无关。
Background: It has been speculated that host macrophages contribute to rapid clearance of transplanted xenogeneic cells. To address such a possibility, phagocytotic and cytolytic activities of human macrophages toward xenogeneic porcine cells were evaluated in vitro in the absence of antibodies and complement factors.Methods: Human peripheral monocyte-derived macrophages (P-macrophages) and reticulo-endothelial macrophages (RE-macrophages) were obtained from volunteers' peripheral blood and from the perfusion effluents of liver allografts for transplantation, respectively. 5-(and 6-) carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled human autologous red blood cells (auto-RBCs), ABO-incompatible RBCs (incom-RBCs) and xenogeneic porcine RBCs (xeno-RBCs) were incubated with the human macrophages; subsequently, the macrophages that had phagocytosed the RBCs could be identified as CFSE positive cells by FCM analyses and confocal microscopy. Cytolytic activity was quantified by calculating levels of lactate dehydrogenase in each culture supernatant.Results: Human RE-macrophages spontaneously phagocytosed and had a remarkable cytolytic activity toward xeno-RBCs, but not toward auto-RBCs or incom-RBCs. Elimination of alpha-galactosyl xenoantigen (alpha-Gal) epitopes on xeno-RBCs did not prevent phagocytotic or cytolytic activity of RE-macrophages.Conclusions: These findings indicate phagocytotic and cytolitic activities of human macrophages toward porcine cells are initiated by a factor other than alpha-Gal in a mechanism independent of antibody/complement opsonization.