ENDOTHELIAL-CELL CONTACT POTENTIATES RELEASE OF SOLUBLE TUMOR-NECROSIS-FACTOR (TNF) RECEPTORS FROM THE MONOCYTE-LIKE CELL-LINE THP-1

The two tumor necrosis factor (TNF) receptors can undergo proteolytic cleavage to form soluble receptors, TNF-R55-BP and TNF-R75-BP, that ca n neutralize TNF, The aim was to study the release of soluble TNF rece ptor forms during monocyte-endothelial cell interaction, Monocytic THP -1 cells were used, and their release of TNF-R75-BP was determined, Co ntact between THP-1 cells and confluent endothelial cells induced four fold higher release of TNF-R75-BP from the THP-1 cells than with these cells in suspension, The release was further increased up to eightfol d after prestimulation of the endothelial cells with interleukin-1 bet a (IL-1 beta), Prestimulation for 10 min gave maximal release of TNF-R 75-BP from the attached THP-1 cells, IL-IP by itself did not induce sh edding of soluble TNF receptors in THP-1 cells, Blocking antibodies ag ainst the endothelial cell adhesion molecules VCAM, ICAM, and E-select in did not affect the release of TNF-R75-BP from THP-I cells attached to the endothelium, Conditioned medium from IL-1 beta-stimulated endot helial cells increased the production of TNF-R75-BP from THP-1 cells i n suspension, However, surface contact between endothelial cells and T HP-1 cells was necessary for maximal production of TNF-R75-BP, TNF-alp ha released from endothelial cells on IL-1 beta stimulation did not pr omote shedding of TNF-R75 from THP-1 cells, Thus, endothelial cell con tact potentiates the production of TNF-R75-BP in a monocyte-like cell line, The shedding of soluble TNF receptors observed in this case seem s to be a result of both cell attachment and soluble factors.