Ishii Y, Shuyi W, Kitamura S
Department of Pulmonary Medicine, Jichi Medical School, Tochigi, Japan.
Life Sci. 1995;56(25):2263-72. doi: 10.1016/0024-3205(95)00216-s.
Lipopolysaccharide (LPS) is a mediator of septic shock and acute respiratory distress syndrome (ARDS), conditions which are characterized by high-permeability pulmonary edema. LPS increases endothelial permeability both directly and indirectly via the pro-inflammatory cytokines produced by monocytes and macrophages. We investigated the role of soluble CD14 in serum in the increased endothelial permeability induced by LPS. Bovine pulmonary artery endothelial cells were grown to confluence on a microporous filter and the 125I-albumin clearance rate across the monolayer was determined. Even a high concentration of LPS (1 microgram/ml) did not increase endothelial permeability under a serum-free condition. In the presence of more than 3% normal human serum, LPS increased endothelial permeability. The presence of neutralizing anti-CD14 monoclonal antibody eliminated the serum-dependent effect of LPS. The addition of recombinant sCD14 completely replaced the requirement for serum. LPS-binding protein (LBP) did not enhance the rsCD14-mediated LPS effect, and anti-LBP antibody did not attenuate the serum-dependent LPS effect. These findings suggest that sCD14 in serum mediates the permeability-increasing effect on LPS on endothelial cells but that LBP is not necessary for this effect.
脂多糖（LPS）是脓毒症休克和急性呼吸窘迫综合征（ARDS）的介质，这些病症的特征是高通透性肺水肿。LPS通过单核细胞和巨噬细胞产生的促炎细胞因子直接或间接增加内皮细胞通透性。我们研究了血清中可溶性CD14在LPS诱导的内皮细胞通透性增加中的作用。牛肺动脉内皮细胞在微孔滤膜上生长至汇合，测定单层上的125I-白蛋白清除率。即使在无血清条件下，高浓度的LPS（1微克/毫升）也不会增加内皮细胞通透性。在存在超过3%的正常人血清时，LPS会增加内皮细胞通透性。中和抗CD14单克隆抗体的存在消除了LPS的血清依赖性效应。添加重组sCD14完全替代了对血清的需求。LPS结合蛋白（LBP）不会增强rsCD14介导的LPS效应，抗LBP抗体也不会减弱血清依赖性LPS效应。这些发现表明，血清中的sCD14介导了LPS对内皮细胞的通透性增加效应，但LBP对于此效应并非必需。
