Suppression of xenogeneic innate immune response by a membrane-type human surfactant protein-A.
Suppression of xenogeneic innate immune response by a membrane-type human surfactant protein-A.
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DOI：
10.3892/etm.2022.11527
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发表时间：
2022-07
影响因子：
2.7
通讯作者：
Chiyoshi Toyama;A. Maeda;Shuhei Kogata;Riho Yamamoto;Kazunori Masahata;T. Ueno;Masafumi Kamiyama;Y. Tazuke;H. Eguchi;H. Okuyama;S. Miyagawa
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作者：
Chiyoshi Toyama;A. Maeda;Shuhei Kogata;Riho Yamamoto;Kazunori Masahata;T. Ueno;Masafumi Kamiyama;Y. Tazuke;H. Eguchi;H. Okuyama;S. Miyagawa
巨噬细胞介导的异种排斥是主要的免疫障碍。我们最近报道猪内皮细胞（SEC）上的膜型表面活性蛋白-D（SP-D）抑制了巨噬细胞介导的排斥反应。与 SP-D 类似，表面活性剂蛋白 A (SP-A) 的碳水化合物识别结构域可以在效应细胞中诱导抑制信号。本研究旨在探讨 SP-A 对巨噬细胞介导的异种排斥的抑制作用。将初始 SEC 和 SPA 转染的 SEC (SEC/SP-A) 与 THP-1 细胞共培养，并评估细胞毒性。为了研究 SP-A 对吞噬作用的影响，将人巨噬细胞与 SEC 或 SEC/SP-A 共培养，并通过流式细胞术评估吞噬作用和活性氧产生的程度。使用逆转录-PCR 测定巨噬细胞中炎症细胞因子的 mRNA 表达水平。此外，还评估了 THP-1-Lucia NF-κB 细胞对转录因子的影响。与naive SEC相比，SEC/SP-A的细胞毒性和吞噬作用显着降低。此外，人巨噬细胞与SEC/SP-A共培养降低了活性氧的产生，并且巨噬细胞中TNFα的mRNA表达水平降低，而IL-10的mRNA表达水平升高。此外，与SEC相比，SEC/SP-A中的NF-κB转录减少。总之，人 SP-A 在猪细胞中的异位表达是抑制巨噬细胞介导的细胞毒性的一种有吸引力的方法。
Macrophage-mediated xenogeneic rejection is a major immunological obstacle. We recently reported that membrane-type surfactant protein-D (SP-D) on swine endothelial cells (SECs) suppressed macrophage-mediated rejection. Similar to SP-D, the carbohydrate recognition domain of surfactant protein-A (SP-A) can induce inhibitory signals in effector cells. The present study aimed to examine the suppressive effect of SP-A on macrophage-mediated xenogeneic rejection. Naive SECs and SPA-transfected SECs (SEC/SP-A) were co-cultured with THP-1 cells and cytotoxicity was evaluated. To investigate the effect of SP-A on phagocytosis, human macrophages were co-cultured with SEC or SEC/SP-A, and the extent of phagocytosis and production of reactive oxygen species were assessed via flow cytometry. The mRNA expression levels of inflammatory cytokines in macrophages were determined using reverse transcription-PCR. Additionally, the effects of THP-1-Lucia NF-κB cells on transcription factors were evaluated. The cytotoxicity and phagocytosis of SEC/SP-A were significantly decreased compared with those of naive SEC. Furthermore, the co-culture of human macrophages with SEC/SP-A decreased reactive oxygen species production, and the mRNA expression levels of TNFα were decreased in macrophages, whereas those of IL-10 were increased. In addition, NF-κB transcription was decreased in SEC/SP-A compared with that in SEC. In conclusion, the ectopic expression of human SP-A in porcine cells represents an attractive method for suppressing macrophage-mediated cytotoxicity.