Receptor Binding and Activation of Polymorphonuclear Neutrophils by Tumor Necrosis Factor-Alpha

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Abstract
The interaction of highly purified recombinant human tumor necrosis factor-alpha (rTNF-α) with human polymorphonuclear neutrophils (PMNs) was investigated. Binding of 125l-rTNF-α to PMN reached maximum levels in 30 min at 37°C and in 2 h at 4°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°C indicated a rapid internalization of rTNF-α. Following this receptor-mediated interaction, recombinant TNF-α 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-α-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-α as an activator of PMN functions and indicate that PMN/TNF-α/endothelial cell interactions may play a major role in inflammatory reactions.

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