Betticher D C, Keller H, Maly F E, Reinhart W H
Department of Internal Medicine, University of Bern, Inselspital, Switzerland.
Br J Haematol. 1993 Jan;83(1):130-7. doi: 10.1111/j.1365-2141.1993.tb04643.x.
Microcirculatory disorders are a common finding in sepsis. We have analysed the influence of two factors released in sepsis, endotoxin and tumour necrosis factor (TNF), on rheological properties of blood cells. The deformability of mixed cell suspensions, isolated erythrocytes, mononuclear cells, or polymorphonuclear leucocytes exposed to endotoxin and TNF in vitro was assessed by filtration through pores of different sizes. Mixed blood cell suspensions showed an increase in cell rigidity when incubated with 100 ng/ml endotoxin. The filtration resistance of isolated erythrocytes, mononuclear or polymorphonuclear leucocytes was not affected by endotoxin. Incubation with TNF in physiological concentrations increased the rigidity of mixed blood cells and of isolated polymorphonuclear leucocytes in a dose- and time-dependent manner, while erythrocytes and mononuclear leucocytes remained unaffected. Polymorphonuclear cells showed decreased deformability associated with shape changes (polarized and non-polar cells with surface protrusions and a shift of F-actin into protrusions). The decrease in deformability was reversed by cytochalasin B or xanthin derivatives such as pentoxifylline. We conclude that TNF decreases the passive deformability of polymorphonuclear leucocytes, which may affect the microcirculation in sepsis. The reversibility with xanthin derivatives may represent a new therapeutic approach for the high morbidity and mortality in sepsis.
微循环障碍是脓毒症中常见的表现。我们分析了脓毒症中释放的两种因子——内毒素和肿瘤坏死因子（TNF）——对血细胞流变学特性的影响。通过不同大小孔径的过滤来评估体外暴露于内毒素和TNF的混合细胞悬液、分离的红细胞、单核细胞或多形核白细胞的变形能力。混合血细胞悬液与100 ng/ml内毒素孵育时，细胞刚性增加。内毒素对分离的红细胞、单核细胞或多形核白细胞的过滤阻力没有影响。生理浓度的TNF孵育以剂量和时间依赖性方式增加了混合血细胞和分离的多形核白细胞的刚性，而红细胞和单核白细胞则不受影响。多形核细胞显示出与形状变化相关的变形能力下降（具有表面突起的极化和非极化细胞以及F-肌动蛋白向突起的转移）。细胞松弛素B或黄嘌呤衍生物如己酮可可碱可逆转变形能力的下降。我们得出结论，TNF降低了多形核白细胞的被动变形能力，这可能会影响脓毒症中的微循环。黄嘌呤衍生物的可逆性可能代表了一种针对脓毒症高发病率和死亡率的新治疗方法。
