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内皮细胞和上皮细胞对肽聚糖与可溶性CD14的复合物无反应,但可被肽聚糖诱导的单核细胞产生的肿瘤坏死因子-α和白细胞介素-1间接激活。

Endothelial and epithelial cells do not respond to complexes of peptidoglycan with soluble CD14 but are activated indirectly by peptidoglycan-induced tumor necrosis factor-alpha and interleukin-1 from monocytes.

作者信息

Jin Y, Gupta D, Dziarski R

机构信息

Northwest Center for Medical Education, Indiana University School of Medicine, Gary 46408, USA.

出版信息

J Infect Dis. 1998 Jun;177(6):1629-38. doi: 10.1086/515318.

DOI:10.1086/515318
PMID:9607843
Abstract

Peptidoglycan (PGN) activates macrophages through membrane CD14 (an endotoxin receptor) and binds to both soluble and membrane CD14. Since soluble CD14-lipopolysaccharide (LPS) complexes activate CD14-negative endothelial and epithelial cells, this study tested whether soluble CD14-PGN complexes activate human umbilical vein endothelial cells and epithelial-like U373 cells to secrete interleukin (IL)-6, express vascular cellular adhesion molecule-1, and translocate nuclear factor-kappaB. In contrast to LPS, endothelial, epithelial, and other cells of non-hemopoietic origin were unresponsive to PGN through soluble or membrane-bound CD14, whereas cells of hemopoietic origin were responsive to both PGN and LPS. PGN, similarly to LPS, activated endothelial and epithelial cells indirectly in the presence of 2%-4% blood, by inducing secretion of both tumor necrosis factor-alpha and IL-1 from monocytes. These results reveal different mechanisms of CD14 function and cell activation for LPS and PGN and also demonstrate strong indirect activation of endothelial and epithelial cells by both PGN and LPS.

摘要

肽聚糖(PGN)通过膜型CD14(一种内毒素受体)激活巨噬细胞,并与可溶性和膜型CD14结合。由于可溶性CD14-脂多糖(LPS)复合物可激活CD14阴性的内皮细胞和上皮细胞,本研究检测了可溶性CD14-PGN复合物是否能激活人脐静脉内皮细胞和上皮样U373细胞分泌白细胞介素(IL)-6、表达血管细胞黏附分子-1以及使核因子-κB发生易位。与LPS不同,非造血来源的内皮细胞、上皮细胞及其他细胞对通过可溶性或膜结合型CD14的PGN无反应,而造血来源的细胞对PGN和LPS均有反应。与LPS相似,PGN在存在2%-4%血液的情况下,通过诱导单核细胞分泌肿瘤坏死因子-α和IL-1,间接激活内皮细胞和上皮细胞。这些结果揭示了LPS和PGN在CD14功能及细胞激活方面的不同机制,同时也证明了PGN和LPS对内皮细胞和上皮细胞均有强烈的间接激活作用。

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