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.
Pichyangkul
S
S
Department of Immunotherapy, Cancer Center at Wadley Institutes, Dallas, Texas 75235.
Schick
D
D
Jia
F L
FL
Berent
S
S
Bollon
A
A
Kahn
A
A
D001310:Auranofin / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D006801:Humans; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D001310:Auranofin