The effect of endotoxin and tumour necrosis factor on erythrocyte and leucocyte deformability in vitro.
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.
Betticher
D C
DC
Department of Internal Medicine, University of Bern, Inselspital, Switzerland.
Keller
H
H
Maly
F E
FE
Reinhart
W H
WH
D004731:Endotoxins / Q000494:pharmacology*; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004912:Erythrocytes / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects*; D008854:Microscopy, Electron; D009504:Neutrophils / Q000648:ultrastructure; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha