Toll-like receptors stimulate human neutrophil function
Toll-like receptors stimulate human neutrophil function
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DOI：
10.1182/blood-2003-04-1078
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发表时间：
2003-10-01
期刊：
影响因子：
20.3
通讯作者：
Luster, AD
中科院分区：
文献类型：
--
作者：
Hayashi, F;Means, TK;Luster, AD
第一个到达感染部位的免疫细胞是中性粒细胞。到达后，中性粒细胞迅速启动杀微生物功能，包括产生抗菌产品和促炎细胞因子；用来控制感染。这使得获得性免疫系统有足够的时间产生消毒免疫和记忆。中性粒细胞通过生殖系编码受体识别微生物相关的分子模式来检测病原体的存在。在脊椎动物中，这些受体最具特征的是toll样受体（TLRs）。我们已经确定了tlr在新鲜分离的人中性粒细胞中的表达和功能。中性粒细胞表达TLR1、2、4、5、6、7、8、9和10-除TILR3外的所有tlr。粒细胞-巨噬细胞集落刺激因子（GM-CSF）处理增加了TLR2和TLR9的表达水平。在中性粒细胞中表达的所有TLRs的激动剂触发或启动细胞因子释放，超氧化物产生和l -选择素脱落，同时抑制对白细胞介素-8 （IL-8）的趋化性并增加活化乳胶珠的吞噬。对TLR9激动剂非甲基化CpG基序DNA （CpG DNA）的反应需要GM-CSF预处理，这也增强了对其他TLR激动剂的反应。最后，使用定量聚合酶链反应（QPCR），我们证明了趋化因子表达谱，表明tlr刺激的中性粒细胞招募先天而非获得性免疫细胞到感染部位。(C) 2003年由美国血液病学会出版。
The first immune cell to arrive at the site of infection is the neutrophil. Upon arrival, neutrophils quickly initiate microbicidal functions, including the production of antimicrobial products and proinflammatory cytokines; that serve to contain infection. This allows the acquired immune system enough time to generate sterilizing immunity and memory. Neutrophils detect the presence of a pathogen through germ line-encoded receptors that recognize microbe-associated molecular patterns. In vertebrates, the best characterized of these receptors are Toll-like receptors (TLRs). We have determined the expression and function of TLRs in freshly isolated human neutrophils. Neutrophils expressed TLR1, 2, 4, 5, 6, 7, 8, 9, and 10-all the TLRs except TILR3. Granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment increased TLR2 and TLR9 expression levels. The agonists of all TLRs expressed in neutrophils triggered or primed cytokine release, superoxide generation, and L-selectin shedding, while inhibiting chemotaxis to interleukin-8 (IL-8) and increasing phagocytosis of opsonized latex beads. The response to the TLR9 agonist nonmethylated CpG-motif-containing DNA (CpG DNA) required GM-CSF pretreatment, which also enhanced the response to the other TLR agonists. Finally, using quantitative polymerase chain reaction (QPCR), we demonstrate a chemokine expression profile that suggests that TLR-stimulated neutrophils recruit innate, but not acquired, immune cells to sites of infection. (C) 2003 by The American Society of Hematology.