Receptor binding and activation of polymorphonuclear neutrophils by tumor necrosis factor-alpha.
The interaction of highly purified recombinant human tumor necrosis factor-alpha (rTNF-alpha) with human polymorphonuclear neutrophils (PMNs) was investigated. Binding of 125I-rTNF-alpha to PMN reached maximum levels in 30 min at 37 degrees C and in 2 h at 4 degrees C. Scatchard analysis of competitive binding data indicated approximately 6000 receptor sites per cell and a Kd of 1.37 nM. Binding data at 37 degrees C indicated a rapid internalization of rTNF-alpha. Following this receptor-mediated interaction, recombinant TNF-alpha was found to inhibit the migration of PMNs under agarose and to enhance PMN production of superoxide anion (O-2) in a dose-dependent manner. Furthermore, rTNF-alpha-activated PMNs caused a marked disruption of human umbilical-vein-derived endothelial cell monolayers and caused inhibition of their proliferative activities. These data substantiate the role of TNF-alpha as an activator of PMN functions and indicate that PMN/TNF-alpha/endothelial cell interactions may play a major role in inflammatory reactions.
D001667:Binding, Competitive; D002455:Cell Division; D002465:Cell Movement; D004727:Endothelium / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D007371:Interferon-gamma