Fibrinogen degradation product fragment D increases endothelial monolayer permeability.
Fibrinogen degradation product fragment D increases endothelial monolayer permeability.
复制标题
纤维蛋白原降解产物片段 D 增加内皮单层通透性。
DOI：
10.1152/ajplung.1991.261.4.l283
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Malik,AB
中科院分区：
文献类型：
--
作者：
Ge,M;Ryan,TJ;Lum,H;Malik,AB
我们评估了两种主要的高分子量纤维蛋白原降解产物(FDP)片段D和E对肺血管内皮细胞屏障功能的影响。用QAE Sephadex柱层析和凝胶过滤将D和E片段纯化为均一。0.5-2.0微米的D片段与牛肺内皮细胞单层孵育2小时后，125I-白蛋白透过率(125I-白蛋白通透性)增加一倍。片段E在浓度为4.0微米时仅使~(125)I-白蛋白清除率增加0.6倍。两种FDP在含血清的孵育液中均保持活性。碎片D的通透性增加作用是可逆的，不是由于细胞脱落或溶解。这种片断-D效应具有时间依赖性，并与内皮F-肌动蛋白微丝的重新分布有关。这种作用与片段D的羧基末端序列无关。片段D和E与肺动脉内皮细胞的结合是特异的和可逆的，但片段D的结合比片段E大3倍，这可能是D片段介导的更大的通透性增加的原因。结果表明，FDP尤其是片段D增加了内皮对白蛋白的通透性。这种反应包括片段D与内皮细胞的特异性结合和细胞内肌动蛋白的重新分布。
We assessed the effects of the two primary high-molecular-weight fibrinogen degradation products (FDP), fragments D and E, on the pulmonary vascular endothelial barrier function. Fragments D and E were purified to homogeneity by QAE Sephadex chromatography followed by gel filtration. Incubation of bovine pulmonary artery endothelial monolayers with 0.5–2.0 microM fragment D for 2 h caused a doubling of transendothelial 125I-albumin clearance rate (a measure of 125I-albumin permeability). Fragment E only produced a 0.6-fold increase in 125I-albumin clearance rate at concentration of 4.0 microM. Both FDP remained active in incubating media with serum. The permeability-increasing effect of fragment D was reversible and was not due to cell detachment or lysis. The fragment-D effect was time dependent and was associated with redistribution of endothelial F-actin microfilaments. The effect was independent of the carboxy-terminal sequence on gamma-chain of fragment D. Fragments D and E binding to pulmonary artery endothelial cells was specific and reversible, but fragment D binding was three-fold greater than fragment E, which may account for the greater permeability increase mediated by fragment D. The results indicate that FDP, especially fragment D, increase endothelial permeability to albumin. The response involves specific binding of fragment D to endothelial cells and redistribution of intracellular actin.