Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: A critical role for monocytes in leukocyte lipopolysaccharide responses
Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: A critical role for monocytes in leukocyte lipopolysaccharide responses
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DOI：
10.4049/jimmunol.168.9.4701
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发表时间：
2002-05-01
影响因子：
4.4
通讯作者：
Dower, SK
中科院分区：
文献类型：
--
作者：
Sabroe, I;Jones, EC;Dower, SK
白细胞对LPS的反应性依赖于CD14和Toll样受体（TLR）家族的受体。中性粒细胞对LPS有反应，但关于嗜酸性粒细胞和嗜碱性粒细胞的LPS反应存在矛盾的数据，并且这些粒细胞谱系中TLR在蛋白质水平上的表达尚未完全描述。我们检测了TLR2、TLR4和CD14的表达，发现单核细胞表达相对高水平的细胞表面TLR2、TLR4和CD14，而中性粒细胞也表达所有三种分子，但水平较低。相反，嗜碱性粒细胞表达TLR2和TLR4，但不表达CD14，而嗜酸性粒细胞不表达这些蛋白质。在一系列功能测定（包括L-选择素脱落、CD11b上调、IL-8 mRNA产生和细胞存活）中，中性粒细胞对LPS有反应，但嗜酸性粒细胞和嗜碱性粒细胞无反应。与以前的数据相反，我们发现，使用负磁选择的单核细胞耗竭，中性粒细胞对LPS的反应在很大程度上依赖于非常低水平的单核细胞的存在，LPS诱导的中性粒细胞存活在22小时是单核细胞依赖性的。我们的结论是，LPS在调节外周血嗜酸性粒细胞和嗜碱性粒细胞功能的作用不大，而且，即使在中性粒细胞，单核细胞编排许多以前观察到的白细胞LPS反应模式。
Leukocyte responsiveness to LPS is dependent upon CD14 and receptors of the Toll-like receptor (TLR) family. Neutrophils respond to LPS, but conflicting data exist regarding LPS responses of eosinophils and basophils, and expression of TLRs at the protein level in these granulocyte lineages has not been fully described. We examined the expression of TLR2, TLR4, and CD14 and found that monocytes expressed relatively high levels of cell surface TLR2, TLR4, and CD14, while neutrophils also expressed all three molecules, but at low levels. In contrast, basophils expressed TLR2 and TLR4 but not CD14, while eosinophils expressed none of these proteins. Tested in a range of functional assays including L-selectin shedding, CD11b up-regulation, IL-8 mRNA generation, and cell survival, neutrophils responded to LPS, but eosinophils and basophils did not. In contrast to previous data, we found, using monocyte depletion by negative magnetic selection, that neutrophil responses to LPS were heavily dependent upon the presence of a very low level of monocytes, and neutrophil survival induced by LPS at 22 h was monocyte dependent. We conclude that LPS has little role in the regulation of peripheral blood eosinophil and basophil function, and that, even in neutrophils, monocytes orchestrate many previously observed leukocyte LPS response patterns.