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The Journal of Immunology, Vol 145, Issue 6 1713-1718, Copyright © 1990 by American Association of Immunologists

ARTICLES

IFN-alpha in vivo enhances tumor necrosis factor receptor levels on hairy cells

C Billard, F Sigaux and J Wietzerbin
Unite de Recherches sur les Interferons, INSERM U. 196, Institut Curie, Paris, France.

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.


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P. K. Baker, A. R. Pettitt, J. R. Slupsky, H. J. Chen, M. A. Glenn, M. Zuzel, and J. C. Cawley
Response of hairy cells to IFN-alpha involves induction of apoptosis through autocrine TNF-alpha and protection by adhesion
Blood, June 28, 2002; 100(2): 647 - 653.
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