RESUMEN
Although xenografts are one of the most attractive strategies for overcoming the shortage of organ donors, cellular rejection by macrophages is a substantial impediment to this procedure. It is well known that macrophages mediate robust immune responses in xenografts. Macrophages also express various inhibitory receptors that regulate their immunological function. Recent studies have shown that the overexpression of inhibitory ligands on porcine target cells results in the phosphorylation of tyrosine residues on intracellular immunoreceptor tyrosine-based inhibitory motifs on macrophages, leading to the suppression of xenogenic rejection by macrophages. It has also been reported that myeloid-derived suppressor cells, a heterogeneous population of immature myeloid cells, suppress not only NK and cytotoxic T lymphocyte cytotoxicity but also macrophage-mediated cytotoxicity. This review is focused on the recent findings regarding strategies for inhibiting xenogenic rejection by macrophages.
Asunto(s)
Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Inmunidad Celular , Macrófagos/inmunología , Trasplante Heterólogo/efectos adversos , Animales , Antígeno CD47/genética , Antígeno CD47/inmunología , Antígeno CD47/metabolismo , Rechazo de Injerto/genética , Rechazo de Injerto/inmunología , Rechazo de Injerto/metabolismo , Xenoinjertos/inmunología , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Macrófagos/metabolismo , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Células Supresoras de Origen Mieloide/trasplante , Fagocitosis , Proteína D Asociada a Surfactante Pulmonar/genética , Proteína D Asociada a Surfactante Pulmonar/inmunología , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Sialiltransferasas/genética , Sialiltransferasas/inmunología , Sialiltransferasas/metabolismo , Transducción de Señal , Resultado del Tratamiento , beta-D-Galactósido alfa 2-6-SialiltransferasaRESUMEN
PURPOSE: Various strategies, such as the generation of alpha-1,3-galactosyltransferase knocked-out pigs and CD55 transgenic pigs, have been investigated to inhibit pig to human xenogeneic rejection. Our aim is to develop strategies to overcome the hurdle of not only hyper acute rejection, but also that of cellular xenogeneic rejection (CXR). Although macrophages have been well known to play a critical role in CXR, monocyte/macrophage-mediated xenogeneic rejection has not been well studied. In this study, we evaluated the effect of CD200 in xenogeneic rejection by macrophages. METHODS: Naïve swine endothelial cells (SEC) and SEC/CD200 were co-cultured with M0 macrophages and the cytotoxicity was measured by a WST-8 assay. The phagocytosis of SEC and SEC/CD200 by macrophages was analyzed by flow cytometry. RESULTS: While CD200 failed to suppress a significant amount of cytotoxicity against SEC by monocytes, M0 macrophage-mediated cytotoxicity was significantly suppressed by human CD200. The phagocytosis by M0 macrophages was also tested. The phagocytosis assay revealed that human CD200 suppresses M0 macrophage-mediated phagocytosis. CONCLUSIONS: Our findings indicate that human CD200 suppresses the xenogeneic rejection by CD200R+ macrophages and that the generation of hCD200 transgenic pigs for use in xenografts is very attractive for preventing the macrophage-mediated rejection.
Asunto(s)
Antígenos CD/fisiología , Citotoxicidad Inmunológica/genética , Células Endoteliales/inmunología , Macrófagos/inmunología , Fagocitosis/genética , Animales , Células Cultivadas , Citometría de Flujo , Rechazo de Injerto/genética , Rechazo de Injerto/inmunología , Humanos , PorcinosRESUMEN
In the original publication, the fifth author name was erroneously published as "Patmika Jiaravuthiasan". The correct author name should read as, "Patmika Jiaravuthisan". The original article was corrected.
