Park Hae-Young, Jin Jun-O, Song Min-Gyu, Park Joo-In, Kwak Jong-Young
Department of Biochemistry, School of Medicine, Medical Research Center for Cancer Molecular Therapy, Dong-A University, Busan 602-714, Korea.
Exp Mol Med. 2007 Aug 31;39(4):439-49. doi: 10.1038/emm.2007.48.
Neutrophils are also known to acquire the characteristics of dendritic cells (DCs) under the appropriate conditions. In this study, neutrophils were cultivated in vitro in the presence or absence of compounds modulating their survival in an attempt to characterize the expression profile of the DC markers. Higher MHC-II, CD80, CD86, CD83, and CD40 expression levels were detected on the surface of the cultured neutrophils for 24 h than on the freshly isolated cells. The annexin V-positive cells showed a higher expression level of the DC markers than the annexin V-negative cells. The population of neutrophils double stained with annexin V and the DC markers increased after being incubated with agonistic anti-Fas Ab. LPS, the anti-apoptotic compound, decreased the CD86 and MHC-II expression levels but 50-60% of the DC marker-positive cells were detected in the annexin V-positive cells. In contrast, CD80, CD86, CD83, and HLA-DR mRNA levels increased in the GM-CSF-treated neutrophils but not in the anti-Fas Ab-treated neutrophils. T cell proliferation was inhibited by co-culturing them with anti-Fas Ab- or LPS-treated neutrophils at a high neutrophil:T cell ratio. However, the superantigen-mediated T cell proliferation was increased by the LPS-treated neutrophils but decreased by the anti-Fas Ab-treated neutrophils. There was a lower level of interferon-gamma production in the T cells co-cultured with anti-Fas Ab-treated neutrophils than with the LPS-treated neutrophils. This suggests that apoptotic neutrophils express DC markers on their surface and the differential expression of DC markers might have a detrimental effect on the immune reaction.
众所周知，在适当条件下中性粒细胞也会获得树突状细胞（DC）的特征。在本研究中，中性粒细胞在有或没有调节其存活的化合物存在的情况下进行体外培养，以试图表征DC标志物的表达谱。培养24小时的中性粒细胞表面检测到的MHC-II、CD80、CD86、CD83和CD40表达水平高于新鲜分离的细胞。膜联蛋白V阳性细胞比膜联蛋白V阴性细胞显示出更高的DC标志物表达水平。用抗Fas激动性抗体孵育后，膜联蛋白V和DC标志物双染的中性粒细胞群体增加。抗凋亡化合物脂多糖（LPS）降低了CD86和MHC-II的表达水平，但在膜联蛋白V阳性细胞中检测到50-60%的DC标志物阳性细胞。相比之下，粒细胞-巨噬细胞集落刺激因子（GM-CSF）处理的中性粒细胞中CD80、CD86、CD83和人类白细胞抗原DR（HLA-DR）的mRNA水平升高，而抗Fas抗体处理的中性粒细胞中则没有升高。在高中性粒细胞与T细胞比例下，将T细胞与抗Fas抗体或LPS处理的中性粒细胞共培养可抑制T细胞增殖。然而，超抗原介导的T细胞增殖在LPS处理的中性粒细胞中增加，而在抗Fas抗体处理的中性粒细胞中减少。与LPS处理的中性粒细胞共培养的T细胞中干扰素-γ的产生水平低于与抗Fas抗体处理的中性粒细胞共培养的T细胞。这表明凋亡的中性粒细胞在其表面表达DC标志物，并且DC标志物的差异表达可能对免疫反应产生不利影响。
