Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
Thromb Res. 2011 Apr;127(4):349-55. doi: 10.1016/j.thromres.2010.12.008. Epub 2011 Jan 13.
An alternative pathway for fibrinolysis that comprises leukocyte elastase and its interaction with the plasminogen activator-plasmin system has been suggested. Plasma levels of cross-linked fibrin degradation product by leukocyte elastase (e-XDP) were significantly increased in patients with sepsis induced disseminated intravascular coagulation (DIC) compared with healthy subjects (18.6±19.9 vs 0.58±0.47U/mL, p<0.001). Twenty seven unique spots were identified from e-XDP dominant patients by immune-purification and two-dimensional difference gel electrophoresis, and they contained fibrinogen Bβ-chain derived fragments Bβ Asp-164, Ser-200, Gln-301, Ala-354, Ile-484 and γ-chain derivatives γ Val-274 at their amino-termini by acquired and processed tandem mass spectrometer. The Sequential Organ Failure Assessment Scores in patients with e-XDPs levels 3-10U/mL were significantly lower than those with e-XDPs levels -3U/mL, 10-30U/mL, and 30- U/mL. The adjusted odds for 28-day mortality rate in patients with e-XDP levels less than 3U/mL (hazard ratio, 4.432; 95% CI, 1.557-12.615 [p=0.005]) were significantly higher than those in patients with e-XDP levels of 3-10U/mL. These data suggest that leukocyte elastase might contribute to the degradation of cross-linked fibrin in sepsis-induced DIC.
已提出纤溶的替代途径，包括白细胞弹性蛋白酶及其与纤溶酶原激活物-纤溶系统的相互作用。与健康受试者相比，脓毒症诱导的弥散性血管内凝血（DIC）患者的白细胞弹性蛋白酶交联纤维蛋白降解产物（e-XDP）的血浆水平显著升高（18.6±19.9 与 0.58±0.47U/mL，p<0.001）。通过免疫纯化和二维差异凝胶电泳从 e-XDP 优势患者中鉴定出 27 个独特斑点，它们在氨基末端包含纤维蛋白原 Bβ 链衍生片段 Bβ Asp-164、Ser-200、Gln-301、Ala-354、Ile-484 和 γ 链衍生物 γ Val-274 通过获得和处理串联质谱仪。e-XDP 水平为 3-10U/mL 的患者的序贯器官衰竭评估评分明显低于 e-XDP 水平为-3U/mL、10-30U/mL 和 30-U/mL 的患者。e-XDP 水平低于 3U/mL（危险比，4.432；95%置信区间，1.557-12.615 [p=0.005]）的患者 28 天死亡率的调整比值明显高于 e-XDP 水平为 3-10U/mL 的患者。这些数据表明，白细胞弹性蛋白酶可能有助于脓毒症诱导的 DIC 中交联纤维蛋白的降解。
