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 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.
Björnberg
F
F
Department of Hematology, University of Lund, Sweden.
Lantz
M
M
D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002448:Cell Adhesion; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility; D053319:Tumor Necrosis Factor Decoy Receptors
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D002352:Carrier Proteins; D007375:Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; D053319:Tumor Necrosis Factor Decoy Receptors; C069521:recombinant human tumor necrosis factor-binding protein-1