Suppression of xenogeneic innate immune response by a membrane‑type human surfactant protein‑A

Toyama,Chiyoshi; Maeda,Akira; Kogata,Shuhei; Yamamoto,Riho; Masahata,Kazunori; Ueno,Takehisa; Kamiyama,Masafumi; Tazuke,Yuko; Eguchi,Hiroshi; Okuyama,Hiroomi; Miyagawa,Shuji

doi:10.3892/etm.2022.11527

Suppression of xenogeneic innate immune response by a membrane‑type human surfactant protein‑A

Authors:
- Chiyoshi Toyama
- Akira Maeda
- Shuhei Kogata
- Riho Yamamoto
- Kazunori Masahata
- Takehisa Ueno
- Masafumi Kamiyama
- Yuko Tazuke
- Hiroshi Eguchi
- Hiroomi Okuyama
- Shuji Miyagawa
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Affiliations: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan
Published online on: July 26, 2022 https://doi.org/10.3892/etm.2022.11527
Article Number: 590

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Abstract

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.

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