ENDOTOXIN-MEDIATED ENDOTHELIAL-CELL INJURY AND ACTIVATION - ROLE OF SOLUBLE CD14
ENDOTOXIN-MEDIATED ENDOTHELIAL-CELL INJURY AND ACTIVATION - ROLE OF SOLUBLE CD14
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DOI：
10.1128/iai.61.8.3149-3156.1993
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发表时间：
1993-08-01
影响因子：
3.1
通讯作者：
KIM, KS
中科院分区：
文献类型：
--
作者：
ARDITI, M;ZHOU, J;KIM, KS
脂多糖（LPS）对血管内皮细胞（EC）的损伤在革兰氏阴性菌脓毒症和内毒素休克的发病机制中起重要作用。本文所述的研究是为了进一步确定EC对LPS反应的分子机制。我们发现，血清是必需的LPS介导的细胞毒性牛脑微血管，肺，主动脉内皮细胞和抗人CD 14抗体完全阻断LPS介导的细胞毒性内皮细胞在人血清的存在下。向无血清培养基中添加重组可溶形式的人CD 14恢复了LPS介导的细胞毒性，而添加LPS结合蛋白（LBP）（一种增强LPS诱导的单核细胞反应的血清蛋白）则没有影响。LPS诱导的人脐静脉内皮细胞分泌白细胞介素-6对血清或重组可溶性CD 14（无血清条件下）的依赖性相似。这些发现表明，可溶性CD 14是必需的LPS介导的EC反应独立的LPB，表明血清可溶性CD 14代表了一种天然存在的激动剂EC响应LPS。
Vascular endothelial cell (EC) injury by lipopolysaccharides (LPS) plays a major role in the pathogenesis of gram-negative bacterial sepsis and endotoxic shock. The studies described here were performed to define further the molecular mechanisms involved in the EC responses to LPS. We showed that serum was required for LPS-mediated cytotoxicity for bovine brain microvessel, pulmonary, and aortic ECs and that anti-human CD14 antibodies completely blocked LPS-mediated cytotoxicity for ECs in the presence of human serum. The addition of a recombinant soluble form of human CD14 to serum-free medium restored the LPS-mediated cytotoxicity, whereas the addition of LPS binding protein (LBP), a serum protein that potentiates LPS-induced responses to monocytes, had no effect. A similar dependency on serum or recombinant soluble CD14 (under serum-free conditions) was observed for LPS-induced secretion of interleukin-6 by human umbilical vein ECs. These findings indicate that soluble CD14 is required for LPS-mediated EC responses independently of LPB, suggesting that serum soluble CD14 represents a naturally occurring agonist for EC responses to LPS.