Granulocyte Colony-Stimulating Factor Improves Deficient In Vitro Neutrophil Transendothelial Migration in Patients with Advanced Liver Disease

Abstract

Bacterial infections are frequent complications in patients with liver cirrhosis. Cirrhotic patients present abnormalities in both innate and adaptive immune responses, including a deficient neutrophil recruitment to infected sites. The purpose of this study was to assess neutrophil-endothelium interactions in cirrhotic patients and evaluate the effects of G-CSF on this process. We studied neutrophil adhesion and transendothelial migration in 14 cirrhotic patients and 14 healthy controls. We also analyzed neutrophil expression of the adhesion molecules CD62L and CD11b in whole blood by flow cytometry. Cirrhotic patients expressed higher levels of CD11b than healthy controls, whereas CD62L expression was significantly lower, suggesting exposure of neutrophils to activating agents within the bloodstream. Neutrophils from cirrhotic patients showed increased adhesion to both resting and tumor necrosis factor alpha-stimulated microvascular endothelial cells and decreased transendothelial migration. Granulocyte colony-stimulating factor (G-CSF) (100 ng/ml) significantly enhanced neutrophil adhesion to microvascular endothelial cells in healthy controls but not in cirrhotic patients. G-CSF also significantly improved neutrophil transmigration in cirrhotic patients and healthy controls. In conclusion, cirrhotic patients exhibit increased neutrophil adhesion to microvascular endothelium and deficient transendothelial migration. G-CSF enhances neutrophil transendothelial migration in cirrhotic patients despite having no effect on neutrophil adhesion. Therefore, G-CSF may be able to increase neutrophil recruitment into infected sites in these patients

Störungen des angeborenen Immunsystems bei akuten und chronischen Lebererkrankungen

“…Colony-stimulating factors: A further, somewhat experimental, approach is the use of granulocyte colony-stimulating factor, which has been shown to improve neutrophil transmigration in patients with advanced cirrhosis [152]. Again, no clinical studies have yet been published.…”

Spontaneous bacterial peritonitis: A severe complication ofliver cirrhosis

“…For proper protection against bacteria, neutrophilic granulocytes have first to adhere to the vascular endothelium, then migrate to the endothelial cellular junctions, pass through by diapedesis and migrate further into the target tissue. Neutrophilic granulocytes of cirrhotic patients adhere to the vascular endothelium to a greater extent and their transendothelial migration is thus decreased [24] . Neutrophilic granulocytes show decreased chemotaxis probably due to the presence of inhibitors of chemotaxis in the blood plasma of the cirrhotic.…”

Stretch-induced human myometrial cytokines enhance immune cell recruitment via endothelial activation

“…Protocol was adapted and modified from Fiuza et al 28 Human UtMVEC-Myo cells were grown in 96-well culture plates (10 000 cells/well) precoated with 0.1% gelatin to form a monolayer for 48 h. After overnight serum starvation, the monolayer was incubated with NS-CM or S-CM for 3 h. Neutrophils were labelled with 2.5 mMcalcein-AM (eBiosciences) for 30 min.…”

“…hUtMVEC-Myo cells were grown in the insert (75 000 cells per 500 ml) to form a monolayer for 72 h. Monolayer confluence was tested measuring its permeability to trypan blue/BSA (adapted from Fiuza et al 28 ). Inserts were washed and transferred into clean wells containing 1 ml HBSS.…”