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

• DOI: 10.1002/jlb.41.3.196
• Publication Date: 2018-01-03T17:55:06Z
• Authors: M R Shalaby; M A Palladino; S E Hirabayashi; T E Eessalu; G D Lewis; H M Shepard; B B Aggarwal
• Keywords: 0301 basic medicine; Neutrophils; Tumor Necrosis Factor-alpha; Receptors, Cell Surface; Binding, Competitive; Monocytes; Receptors, Tumor Necrosis Factor; Recombinant Proteins; 3. Good health; Interferon-gamma; 03 medical and health sciences; Cell Movement; Superoxides; Humans; Endothelium; Lymphocytes; Cell Division; Glycoproteins

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.