title: Endothelial cell contact potentiates release of soluble tumor necrosis factor (TNF) receptors from the monocyte-like cell line THP-1.
abstract: The two tumor necrosis factor (TNF) receptors can undergo proteolytic cleavage to form soluble receptors, TNF-R55-BP and TNF-R75-BP, that can neutralize TNF. The aim was to study the release of soluble TNF receptor forms during monocyte-endothelial cell interaction. Monocytic THP-1 cells were used, and their release of TNF-R75-BP was determined. Contact between THP-1 cells and confluent endothelial cells induced fourfold higher release of TNF-R75-BP from the THP-1 cells than with these cells in suspension. The release was further increased up to eightfold after prestimulation of the endothelial cells with interleukin-1beta (IL-1beta). Prestimulation for 10 min gave maximal release of TNF-R75-BP from the attached THP-1 cells. IL-1beta by itself did not induce shedding of soluble TNF receptors in THP-1 cells. Blocking antibodies against the endothelial cell adhesion molecules VCAM, ICAM, and E-selectin did not affect the release of TNF-R75-BP from THP-1 cells attached to the endothelium. Conditioned medium from IL-1beta-stimulated endothelial cells increased the production of TNF-R75-BP from THP-1 cells in suspension. However, surface contact between endothelial cells and THP-1 cells was necessary for maximal production of TNF-R75-BP. TNF-alpha released from endothelial cells on IL-1beta stimulation did not promote shedding of TNF-R75 from THP-1 cells. Thus, endothelial cell contact potentiates the production of TNF-R75-BP in a monocyte-like cell line. The shedding of soluble TNF receptors observed in this case seems to be a result of both cell attachment and soluble factors.
authors.affiliation: Department of Hematology, University of Lund, Sweden. flemming.bjornberg@eforsk.lu.se
authors.forename: F
authors.initials: F
authors.lastname: Björnberg
authors.forename: M
authors.initials: M
authors.lastname: Lantz
mesh_terms: D000906:Antibodies / Q000097:blood; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000276:immunology; D002460:Cell Line; D017077:Culture Media, Conditioned; D003513:Cycloheximide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012995:Solubility; D013268:Stimulation, Chemical
chemical_list: D000906:Antibodies; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D007375:Interleukin-1; D011500:Protein Synthesis Inhibitors; D018124:Receptors, Tumor Necrosis Factor; D003513:Cycloheximide