IFN-alpha in vivo enhances tumor necrosis factor receptor levels on hairy cells.
Hairy cell leukemia (HCL) is a preplasma B cell neoplasia that is characterized by monocytopenia and responds to IFN-alpha therapy. We investigated the expression of receptors for TNF-alpha, a monocyte-derived cytokine, on the surface of hairy cells from seven HCL patients before and after treating them with IFN-alpha. Iodinated TNF-alpha binding experiments showed the presence of high affinity TNF-alpha receptors in six patients, but no specific binding was detected in the seventh. Scatchard's analysis revealed the presence of a single class of receptors, with 130 to 1200 sites/cell (mean 420) and Kd values of 0.37 to 0.89 nM. The TNF-alpha-R complex was identified by cross-linking as a single band of 94 kDa. Treatment of the patients with 3 x 10(6) U of IFN-alpha 2a markedly increased the number of TNF-alpha-R at 24 or 48 h, without changing the Kd. In the patient who lacked receptor expression on his tumor cells, high affinity TNF-alpha-R were detected at 48 h after IFN injection. These results suggest that in hairy cells, IFN-alpha can interact in vivo with TNF-alpha, through the modulation of TNF-R.
Billard
C
C
Unité de Recherches sur les Interférons, INSERM U. 196, Institut Curie, Paris, France.
Sigaux
F
F
Wietzerbin
J
J
D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D007943:Leukemia, Hairy Cell / Q000378:metabolism* / Q000628:therapy; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism* / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects
D007370:Interferon Type I; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha