重新评估ACKR3在淋巴内皮细胞中的上腺素清除功能
Elena C Sigmund1, Aline Bauer1, Barbara D Jakobs2
1Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
PloS one
|May 30, 2023
概括
非典型的化学因受体3 (ACKR3) 清除化学因,但不会在人类淋巴内皮细胞中内化上腺素 (AM). 独立于ACKR3的机制调解AM对细胞增殖和淋巴细胞增生的影响.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
背景情况:
- 非典型的化学因子受体3 (ACKR3) 作为化学因子和阿片类的清除剂.
- 此外,ACKR3还与上腺素 (AM) 结合,这是一种对心血管功能和胚胎淋巴血管生成至关重要的类激素.
- 缺少ACKR3和过度表达AM的小鼠胚胎表现出淋巴细胞增生,这表明ACKR3在调节AM驱动的淋巴血管生成中的作用.
研究的目的:
- 研究ACKR3在人类淋巴内皮细胞 (LECs) 清除上腺素 (AM) 中的作用.
- 为了确定ACKR3是否调解AM内化和随后的细胞反应.
主要方法:
- 在体外研究中使用了HEK293细胞和人类初级皮肤LEC.
- 用光标记的化学因子和AM进行了联结和内化试验.
- 操纵了ACKR3表达,并共同表达了正规的AM受体 (CALCRL/RAMP2或RAMP3).
主要成果:
- 人类LECs有效地以ACKR3依赖的方式清理了CXCL12和CXCL11/12的仿制化学基因.
- AM诱导LEC扩散,但AM内部化与ACKR3.3独立.
- 在HEK293细胞中宫外ACKR3表达并没有调解AM内化;这需要常规AM受体的共同表达.
结论:
- 人类LECs通过ACKR3-介导的AM清理不会在触发规范AM受体介导反应的度下发生.
- 在AM清理中ACKR3的作用可能不会直接防止AM诱导的淋巴血管生成或由正规受体介导的淋巴细胞增生.
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