Pollack M, Ohl C A, Golenbock D T, Di Padova F, Wahl L M, Koles N L, Guelde G, Monks B G
Department of Medicine, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, Maryland 20814, USA.
J Immunol. 1997 Oct 1;159(7):3519-30.
Human phagocytes recognize bacterial LPS (endotoxin) through membrane CD14 (mCD14), a proinflammatory LPS receptor. This study tested the hypothesis that anti-LPS Abs neutralize endotoxin by blocking cellular uptake through mCD14. Ab-associated changes in the uptake and cellular distribution of FITC-LPS were assessed by flow cytometry and laser scanning confocal microscopy in human CD14-transfected Chinese hamster ovary fibroblasts (CHO-CD14 cells) and human peripheral blood monocytes. LPS core- and O-side chain-specific mAbs inhibited mCD14-mediated LPS uptake by both cell types in the presence of serum. O-side chain-specific mAb concurrently enhanced complement-dependent LPS uptake by monocytes through complement receptor-1 (CR1) and uptake by CHO-CD14 cells involving another heat-labile serum factor(s) and cell-associated recognition molecule(s). Core-specific mAb inhibited mCD14-mediated uptake of homologous and heterologous LPS, while producing less concurrent enhancement of non-mCD14-mediated LPS uptake. The modulation by anti-LPS mAbs of mCD14-mediated LPS uptake was associated with inhibition of LPS-induced nuclear factor-kappaB (NF-kappaB) translocation and TNF-alpha secretion in CHO-CD14 cells and monocytes, respectively, while mAb enhancement of non-mCD14-mediated LPS uptake stimulated these activities. LPS-specific Abs thus mediate anti-inflammatory and proinflammatory functions, respectively, by preventing target cell uptake of LPS through mCD14 and augmenting uptake through CR1 or other cell receptors.
人类吞噬细胞通过膜型CD14（mCD14）识别细菌脂多糖（内毒素），mCD14是一种促炎脂多糖受体。本研究检验了以下假设：抗脂多糖抗体通过阻断mCD14介导的细胞摄取来中和内毒素。通过流式细胞术和激光扫描共聚焦显微镜，在人CD14转染的中国仓鼠卵巢成纤维细胞（CHO-CD14细胞）和人外周血单核细胞中评估抗体相关的异硫氰酸荧光素标记的脂多糖摄取及细胞分布变化。在有血清存在的情况下，脂多糖核心和O侧链特异性单克隆抗体抑制了两种细胞类型中mCD14介导的脂多糖摄取。O侧链特异性单克隆抗体同时增强了单核细胞通过补体受体-1（CR1）的补体依赖性脂多糖摄取以及CHO-CD14细胞通过另一种热不稳定血清因子和细胞相关识别分子的摄取。核心特异性单克隆抗体抑制mCD14介导的同源和异源脂多糖摄取，同时对非mCD14介导的脂多糖摄取的增强作用较小。抗脂多糖单克隆抗体对mCD14介导的脂多糖摄取的调节分别与CHO-CD14细胞和单核细胞中脂多糖诱导的核因子-κB（NF-κB）易位和肿瘤坏死因子-α（TNF-α）分泌的抑制相关，而单克隆抗体对非mCD14介导的脂多糖摄取的增强则刺激了这些活性。因此，脂多糖特异性抗体分别通过阻止靶细胞通过mCD14摄取脂多糖和增强通过CR1或其他细胞受体的摄取来介导抗炎和促炎功能。
