The Inflammatory Cytokine IL-21 is Expressed by Splenic Neutrophils in Response to Transplantation of Allogeneic Cells.
The Inflammatory Cytokine IL-21 is Expressed by Splenic Neutrophils in Response to Transplantation of Allogeneic Cells.
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DOI：
10.15226/2372-0948/4/1/00144
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
J. Thompson;Debra L. Hardin;Judy F Glass;J. Dziba;J. Campion;Stephen P. A. Brown
中科院分区：
文献类型：
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作者：
J. Thompson;Debra L. Hardin;Judy F Glass;J. Dziba;J. Campion;Stephen P. A. Brown
我们之前报道过脾脏中GR-1中性粒细胞/单核细胞急剧上升，在第7天达到峰值，并在第14天下降。这一时期与移植同种异体供体细胞的BALB/c小鼠急性移植物抗宿主病（aGVHD）的高峰期相对应。我们现在问：这些脾脏中性粒细胞/单核细胞在移植后第7天和第14天表达了什么细胞因子？BALB/c小鼠分别移植同种异体B6或同基因BALB/c供体细胞。记录长期生存至第31天。其余各组分别于移植后第3、5、7、14、21、31天处死，记录脾脏细胞总数及表型。在移植B6和BALB/c细胞后的第7天和第14天，从小鼠脾脏中分离出中性粒细胞。同基因移植患者的日体重在第2天出现短暂下降，但在第7天下降幅度更大，达到最低点，31天内从未完全恢复。在所有同种异体移植中，脾脏的CD8/CD4 T淋巴细胞在第5天达到峰值，第7天gr - 1细胞紧随其后。在同基因移植中，淋巴细胞的早期上升没有发生，GR-1细胞在第14天达到峰值。在移植后第7天和第14天分别从脾脏中分离出高纯度的中性粒细胞。在这两个实验中，第7天的异基因中性粒细胞表达白细胞介素-21 (IL-21) mRNA水平显著升高，而第7天和第14天的同基因细胞表达TNFα水平较低但显著。体外刺激前后第7天，异基因中性粒细胞细胞内出现IL-21。结论在同种异体移植GVHD的早期高峰第7天从脾脏分离纯化的中性粒细胞表达高水平的IL-21信息和细胞内IL-21。
We have previously reported that GR-1 neutrophil/monocytes rose dramatically in the spleen, peaked by day 7 and declined through day 14. This period corresponded to the peak of acute Graft-Versus-Host Disease (aGVHD) in BALB/c mice transplanted with allogeneic donor cells. We now asked: what cytokines did these splenic neutrophil/monocytes express on day 7 and 14 post transplant? BALB/c mice were transplanted with allogeneic B6 or syngeneic BALB/c donor cells. Long term survival was recorded through day 31. Other groups were sacrificed on days 3, 5, 7, 14, 21 and 31 days post transplant to record the total number of cells in the spleens and their phenotypes. Neutrophils were isolated from the spleens of mice transplanted with B6 and BALB/c cells on days 7 and 14. Daily body weight demonstrated a transient drop in the syngeneic transplants on day 2 but a much greater drop with its nadir at day 7 and never fully recovering through 31 days. CD8/CD4 T lymphocytes peaked in the spleen on day 5 and were followed on day 7 by GR-I cells in all of the allogeneic transplants. In syngeneic transplants this early rise in lymphocytes did not occur and GR-1 cells peaked on day 14. Highly purified neutrophils were isolated in two separate experiments from the spleens on days 7 and 14 post transplant. In both experiments day 7 allogeneic neutrophils expressed significantly elevated levels of Interleukin-21 (IL-21) mRNA whereas the day 7 and 14 syngeneic cells expressed lower but significant levels of TNFα. Intracellular IL-21 was demonstrated in the allogeneic neutrophils on day 7 before and after in vitro stimulation. In conclusion Purified neutrophils isolated from the spleen on day 7, the early peak of allogeneic transplantation a GVHD, express high levels of IL-21 message and intracellular IL-21.