ADHERENCE TO ENDOTHELIAL-CELLS INDUCES RELEASE OF SOLUBLE TUMOR-NECROSIS-FACTOR (TNF) RECEPTOR FORMS FROM NEUTROPHIL GRANULOCYTES

The TNF receptors, TNF-R55 and TNF-R75, may undergo proteolytic cleava ge and form soluble receptor forms, TNF-R55-BP and TNF-R75-BP. Neutrop hils are abundant with both forms of TNF-receptors, while endothelial cells (ECV 304) only express TNF-R55. Human neutrophils were allowed t o interact with an unstimulated or a IL-1 beta stimulated endothelium followed by determination of TNF-R75-BP with ELISA. Neutrophils in sus pension or in contact with an unstimulated endothelium released only l ow amounts of TNF-R75-BP. However, neutrophils released significant am ounts of TNF-R75-BP after adherence to an endothelium stimulated with IL-1 beta. Neutrophils were not generally activated during adherence s ince concomitant release of lactoferrin from neutrophils only reached levels of 1-5% compared with incubation with phorbolesters. Blocking i ntegrins with antibodies to CD11/CD18 resulted in inhibition of both n eutrophil adherence to an endothelium and shedding of TNF-R75, In addi tion, TNF-R55-BP decreased the production of TNF from IL-1 beta stimul ated endothelial cells, suggesting that soluble TNF receptor forms are able to inhibit TNF production. (C) 1998 Academic Press.