混合CL-SP-D分子有可能比CD47更有效地调节人类中性粒细胞的异源性排斥
Keigo Iemitsu1, Rieko Sakai1, Akira Maeda2
1Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; Meiji University International Institute for Bio-Resource Research, Kawasaki, Kanagawa, Japan.
Transplant immunology
|March 7, 2024
概括
在猪内皮细胞模型中,CL-SP-D有效地抑制了中性粒细胞介导的异体移植排斥,在猪内皮细胞模型中表现优于CD47. 这一发现提供了一种有希望的策略,通过调节先天免疫反应来改善异种移植的结果.
科学领域:
- 免疫学 免疫学 免疫学
- 移植生物学 移植生物学
- 生物化学 生物化学
背景情况:
- 天生的免疫在异种移植中至关重要,CD47-SIRPα相互作用调节免疫细胞细胞毒性.
- 之前的研究表明,CL-P1和表面活性蛋白-D混合体 (CL-SP-D) 通过SIRPα调节巨细胞灭菌.
- 了解中性粒细胞介导的排斥机制对于异种移植的生存至关重要.
研究的目的:
- 研究人类CD47和CL-SP-D在抑制中性粒细胞介导异种移植排斥方面的疗效.
- 为了比较CL-SP-D和CD47对猪内皮细胞 (SECs) 的抑制作用.
- 评估对中性粒细胞毒性,活性氧物种 (ROS) 生产和中性粒细胞外陷 (NET) 形成的影响.
主要方法:
- 在HL-60细胞和初级中性粒细胞上确认了SIRPα的表达.
- 通过等离子体转染产生表达CD47或CL-SP-D的SECs.
- 与HL-60细胞或中性粒细胞共同培养的工程SECs,使用WST-8试验评估细胞毒性.
- 评估了ROS的产生和中性粒细胞NETosis.
主要成果:
- 在HL-60细胞和中性粒细胞中,CL-SP-D显著抑制了细胞毒性.
- CD47抑制了周围血液中性粒细胞的细胞毒性,但不是HL-60细胞.
- CD47和CL-SP-D都显著降低了SEC中的ROS产量.
- CL-SP-D显著抑制了中性粒细胞NET的发生.
结论:
- CL-SP-D在抑制中性粒细胞介导的异原体排斥方面表现出高效.
- 与CD47相比,CL-SP-D在防止中性粒细胞介导的异种移植排斥方面表现出更好的抑制作用.
- CL-SP-D 是缓解异种移植排斥的有希望的治疗候选者.
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