Low density neutrophils (LDN) in postoperative abdominal cavity assist the peritoneal recurrence through the production of neutrophil extracellular traps (NETs).

Low density neutrophils (LDN) in postoperative abdominal cavity assist the peritoneal recurrence through the production of neutrophil extracellular traps (NETs).
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术后腹腔中的低密度中性粒细胞(LDN)通过产生中性粒细胞胞外捕获物(NET)来帮助腹膜复发。

DOI:
10.1038/s41598-017-19091-2
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发表时间:
2018-01-12
期刊:
影响因子:
4.6
通讯作者:
Kitayama J
Kitayama J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kanamaru R;Ohzawa H;Miyato H;Matsumoto S;Haruta H;Kurashina K;Saito S;Hosoya Y;Yamaguchi H;Yamashita H;Seto Y;Lefor AK;Sata N;Kitayama J

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腹部手术后腹腔内出现多种免疫细胞。在因胃癌而接受剖腹手术的患者中,在手术前后获得腹膜灌洗。在Ficoll-Hypaque离心后从中间层回收细胞,并分析表型和功能,特别是关注低密度中性粒细胞(LDN)。与术前灌洗相比,术后具有成熟表型的CD 66 b(+)LDN数量明显增加。纯化的LDN短期培养产生许多线状结构,SYTOX、核酸染色以及组蛋白和髓过氧化物酶阳性,表明NETs形成。人胃癌细胞MKN-45、OCUM-1和NUGC-4选择性地附着在NETs上,而DNA酶I预处理可完全消除这种附着。LDN与MKN 45在裸鼠中的腹膜内(IP)共转移强烈增强腹膜上的转移形成,这被随后的DNA酶I的IP施用强烈抑制。在胃切除术后的人网膜组织表面发现了许多NETs样结构。腹膜表面的NETs可以帮助散布在腹部的游离肿瘤细胞聚集和生长。用DNA酶阻断NETs可能有助于预防腹部手术后腹膜复发。
Many types of immune cells appear in peritoneal cavity after abdominal surgery. In patients who underwent laparotomy due to gastric cancer, peritoneal lavages were obtained before and after surgical procedure. Cells were recovered from intermediate layer after Ficoll-Hypaque centrifugation and analyzed for phenotypes and functions, especially focused on low density neutrophils (LDN). The number of CD66b (+) LDN with mature phenotype was markedly elevated in postoperative as compared with preoperative lavages. Short term culture of the purified LDN produced many threadlike structures positive for SYTOX, nucleic acid staining, as well as histone and myeloperoxidase, suggesting the NETs formation. Human gastric cancer cells, MKN45, OCUM-1 and NUGC-4, were selectively attached on the NETs, which was totally abolished by the pretreatment of DNAse I. Intraperitoneal (IP) co-transfer of the LDN with MKN45 in nude mice strongly augments the metastasis formation on peritoneum, which was strongly suppressed by the following IP administration of DNAse I. Many NETs-like structures were detected on the surface of human omental tissue resected by gastrectomy. NETs on peritoneal surface can assist the clustering and growth of free tumor cells disseminated in abdomen. Disruption of the NETs by DNAse might be useful to prevent the peritoneal recurrence after abdominal surgery.
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