Mandl-Weber S, Haslinger B, Lederer S R, Sitter T
Medizinische Klinik, Klinikum Innenstadt der Universität München, Munich, Germany.
Am J Kidney Dis. 2001 Apr;37(4):815-9. doi: 10.1016/s0272-6386(01)80131-1.
Human peritoneal mesothelial cells (HMCs) have a critical role in maintaining the intraperitoneal balance between fibrinolysis and coagulation by expressing the fibrinolytic enzyme, tissue-type plasminogen activator (tPA), as well as a specific plasminogen activator inhibitor (type 1; PAI-1). During bacterial peritonitis, the balance between intraperitoneal generation and degradation of fibrin is disturbed. As a consequence, severe peritoneal damage occurs, which is one of the leading causes of patient dropout from continuous ambulatory peritoneal dialysis (CAPD) therapy. Cultured HMCs isolated from omental biopsy specimens were used to study the effect of heat-killed strains (2 x 10(8)/mL) of Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli on the synthesis of tPA and PAI-1. Conditioned media were obtained by incubating cells with the different bacterial strains. tPA and PAI-1 antigen concentrations were measured in the cell supernatants by enzyme-linked immunosorbent assay. Each of the three heat-killed microorganisms induced a time-dependent increase in PAI-1 synthesis. After a 48-hour incubation period, the strongest effect was seen in the presence of S aureus (3.5-fold versus control), followed by S epidermidis (2.5-fold versus control) and E coli (1.5-fold versus control). Under the same conditions, tPA antigen levels did not change after exposure to S aureus or E coli, whereas the addition of S epidermidis resulted in enhanced tPA antigen production (2-fold versus control). The increase in PAI-1 synthesis in the presence of the heat-killed microorganisms was preceded by similar changes in interleukin-1alpha (IL-1alpha) levels. Inhibiting the activity of IL-1alpha with a neutralizing antibody significantly reduced bacterial-induced PAI-1 production. Our results indicate that the fibrinolytic imbalance during bacterial peritonitis depends on the bacterial species. The increase in PAI-1 synthesis, not the decrease in the production of tPA, alters mesothelial fibrinolytic activity. Because the increase in PAI-1 expression is significantly quenched by blocking the activity of IL-1alpha, the mesothelial release of this cytokine is involved in bacterial-induced changes in the fibrinolytic system.
人腹膜间皮细胞（HMCs）通过表达纤维蛋白溶解酶、组织型纤溶酶原激活剂（tPA）以及一种特定的纤溶酶原激活剂抑制剂（1型；PAI-1），在维持腹膜内纤维蛋白溶解和凝血之间的平衡中发挥关键作用。在细菌性腹膜炎期间，腹膜内纤维蛋白生成与降解之间的平衡被打破。结果，发生严重的腹膜损伤，这是持续非卧床腹膜透析（CAPD）治疗中患者退出治疗的主要原因之一。从网膜活检标本中分离培养的HMCs用于研究金黄色葡萄球菌、表皮葡萄球菌和大肠杆菌的热灭活菌株（2×10⁸/mL）对tPA和PAI-1合成的影响。通过将细胞与不同细菌菌株孵育获得条件培养基。通过酶联免疫吸附测定法测量细胞上清液中的tPA和PAI-1抗原浓度。三种热灭活微生物中的每一种都诱导PAI-1合成呈时间依赖性增加。在孵育48小时后，在金黄色葡萄球菌存在下观察到最强的作用（相对于对照增加3.5倍），其次是表皮葡萄球菌（相对于对照增加2.5倍）和大肠杆菌（相对于对照增加1.5倍）。在相同条件下，暴露于金黄色葡萄球菌或大肠杆菌后tPA抗原水平没有变化，而添加表皮葡萄球菌导致tPA抗原产生增加（相对于对照增加2倍）。在热灭活微生物存在下PAI-1合成的增加之前，白细胞介素-1α（IL-1α）水平有类似变化。用中和抗体抑制IL-1α的活性可显著降低细菌诱导的PAI-1产生。我们的结果表明，细菌性腹膜炎期间的纤维蛋白溶解失衡取决于细菌种类。PAI-1合成的增加而非tPA产生量的减少改变了间皮纤维蛋白溶解活性。由于通过阻断IL-1α的活性可显著抑制PAI-1表达的增加，因此这种细胞因子的间皮释放参与了细菌诱导的纤维蛋白溶解系统变化。
