Tapping R I, Akashi S, Miyake K, Godowski P J, Tobias P S
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Immunol. 2000 Nov 15;165(10):5780-7. doi: 10.4049/jimmunol.165.10.5780.
Two members of the mammalian Toll-like receptor (TLR) family, TLR2 and TLR4, have been implicated as receptors mediating cellular activation in response to bacterial LPS. Through the use of mAbs raised against human TLR2 and TLR4, we have conducted studies in human cell lines and whole blood to ascertain the relative contribution of these receptors to LPS induced cytokine release. We show that the contribution of TLR2 and TLR4 to LPS-induced cellular activation correlates with the relative expression levels of these two TLRs in a given cell type. In addition, we have found that significant differences in cell stimulatory activity exist between various smooth and rough LPS types that cannot be ascribed to known LPS structural features. These results suggest that impurities in the LPS may be responsible for some of the activity and this would be in agreement with recently published results of others. Upon repurification, none of the commercial LPS preparations activate cells through TLR2, but continue to stimulate cells with comparable activity through TLR4. Our results confirm recent findings that TLR4, but not TLR2, mediates cellular activation in response to LPS derived from both Escherichia coli and Salmonella minnesota. Additionally, we show that TLR4 is the predominant signaling receptor for LPS in human whole blood.
哺乳动物Toll样受体（TLR）家族的两个成员TLR2和TLR4，被认为是介导细胞对细菌脂多糖（LPS）产生反应并激活的受体。通过使用针对人TLR2和TLR4产生的单克隆抗体，我们在人细胞系和全血中进行了研究，以确定这些受体对LPS诱导的细胞因子释放的相对贡献。我们发现，TLR2和TLR4对LPS诱导的细胞激活的贡献与这两种TLR在特定细胞类型中的相对表达水平相关。此外，我们发现，各种光滑型和粗糙型LPS之间存在细胞刺激活性的显著差异，这些差异不能归因于已知的LPS结构特征。这些结果表明，LPS中的杂质可能是某些活性的原因，这与其他人最近发表的结果一致。重新纯化后，没有一种商业LPS制剂通过TLR2激活细胞，但继续以相当的活性通过TLR4刺激细胞。我们的结果证实了最近的发现，即TLR4而非TLR2介导细胞对来自大肠杆菌和明尼苏达沙门氏菌的LPS的激活反应。此外，我们表明TLR4是人类全血中LPS的主要信号受体。
