Adherence to endothelial cells induces release of soluble tumor necrosis factor (TNF) receptor forms from neutrophil...

The TNF receptors, TNF-R55 and TNF-R75, may undergo proteolytic cleavage and form soluble receptor forms, TNF-R55-BP and TNF-R75-BP. Neutrophils are abundant with both forms of TNF-receptors, while endothelial cells (ECV 304) only express TNF-R55. Human neutrophils were allowed to interact with an unstimulated or a IL-1 beta stimulated endothelium followed by determination of TNF-R75-BP with ELISA. Neutrophils in suspension or in contact with an unstimulated endothelium released only low amounts of TNF-R75-BP. However, neutrophils released significant amounts of TNF-R75-BP after adherence to an endothelium stimulated with IL-1 beta. Neutrophils were not generally activated during adherence since concomitant release of lactoferrin from neutrophils only reached levels of 1-5% compared with incubation with phorbolesters. Blocking integrins with antibodies to CD11/CD18 resulted in inhibition of both neutrophil adherence to an endothelium and shedding of TNF-R75. In addition, TNF-R55-BP decreased the production of TNF from IL-1 beta stimulated endothelial cells, suggesting that soluble TNF receptor forms are able to inhibit TNF production.