Medvedev A E, Flo T, Ingalls R R, Golenbock D T, Teti G, Vogel S N, Espevik T
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
J Immunol. 1998 May 1;160(9):4535-42.
This study was undertaken to evaluate the role of CD14 and complement receptors type 3 (CR3) and 4 (CR4) in mediating TNF release and NF-kappaB activation induced by LPS and cell wall preparations from group B streptococci type III (GBS). LPS and GBS caused TNF secretion from human monocytes in a CD14-dependent manner, and soluble CD14, LPS binding protein, or their combination potentiated both LPS- and GBS-induced activities. Blocking of either CD14 or CD18, the common beta-subunit of CR3 and CR4, decreased GBS-induced TNF release, while LPS-mediated TNF production was inhibited by anti-CD14 mAb only. Chinese hamster ovary cell transfectants (CHO) that express human CD14 (CHO/CD14) responded to both LPS and GBS with NF-kappaB translocation, which was inhibited by anti-CD14 mAb and enhanced by LPS binding protein. While LPS showed fast kinetics of NF-kappaB activation in CHO/CD14 cells, a slower NF-kappaB response was induced by GBS. LPS also activated NF-kappaB in CHO cells transfected with either human CR3 or CR4 cDNA, although responses were delayed and weaker than those of CHO/CD14 cells. In contrast to LPS, GBS failed to induce NF-kappaB in CHO/CR3 or CHO/CR4 cells. Both C3H/OuJ (Lps[n]) and C3H/HeJ (Lps[d]) mouse peritoneal macrophages responded to GBS with TNF production and NF-kappaB translocation, whereas LPS was active only in C3H/OuJ macrophages. Thus, LPS and GBS differentially involve CD14 and CR3 or CR4 for signaling NF-kappaB activation in CHO cells and TNF release in human monocytes, and engage a different set of receptors and/or intracellular signaling pathways in mouse macrophages.
本研究旨在评估CD14以及补体3型（CR3）和4型（CR4）受体在介导脂多糖（LPS）和III型B组链球菌（GBS）细胞壁制剂诱导的肿瘤坏死因子（TNF）释放及核因子κB（NF-κB）激活中的作用。LPS和GBS以依赖CD14的方式诱导人单核细胞分泌TNF，可溶性CD14、LPS结合蛋白或它们的组合可增强LPS和GBS诱导的活性。阻断CD14或CR3和CR4的共同β亚基CD18可降低GBS诱导的TNF释放，而LPS介导的TNF产生仅被抗CD14单克隆抗体抑制。表达人CD14的中国仓鼠卵巢细胞转染子（CHO/CD14）对LPS和GBS均有NF-κB易位反应，该反应被抗CD14单克隆抗体抑制，并被LPS结合蛋白增强。虽然LPS在CHO/CD14细胞中显示出快速的NF-κB激活动力学，但GBS诱导的NF-κB反应较慢。LPS也可激活转染了人CR3或CR4 cDNA的CHO细胞中的NF-κB，尽管反应延迟且比CHO/CD14细胞中的反应弱。与LPS相反，GBS未能在CHO/CR3或CHO/CR4细胞中诱导NF-κB。C3H/OuJ（Lps[n]）和C3H/HeJ（Lps[d]）小鼠腹腔巨噬细胞对GBS均有TNF产生和NF-κB易位反应，而LPS仅在C3H/OuJ巨噬细胞中具有活性。因此，LPS和GBS在CHO细胞中激活NF-κB信号以及在人单核细胞中释放TNF时，对CD14和CR3或CR4的依赖方式不同，并且在小鼠巨噬细胞中涉及不同的受体和/或细胞内信号通路。
