Binding of tumor necrosis factor alpha (TNF-alpha) to high-affinity receptors on polymorphonuclear cells

The effects of tumor necrosis factor alpha (TNF-alpha) on human polymorphonuclear (PMN) cells were investigated. We found that 125I-TNF-alpha bound specifically to high-affinity receptors on PMN cells. At 4 degrees C, the binding occurred rapidly and reached steady state after 20 min. The Scatchard plot showed a single class of high-affinity receptors with approximately 2200 receptors/cell and a dissociation constant of 2 x 10(-10) M. There was a linear relationship between TNF-alpha binding and TNF-alpha-induced PMN cell adherence. The concentration of TNF-alpha required to achieve approximately 50% of maximum binding was also approximately the concentration required to reach 50% cell adherence. Auranofin was shown to inhibit TNF-alpha-induced PMN cell adherence at a dose of 5-10 micrograms/ml. This inhibitory effect was not due to the inhibition of TNF-alpha binding to PMN cells by the drug. These observations may have clinical implications.