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Characterization of interleukin-10 receptor expression on B-cell chronic
lymphocytic leukemia cells
J Jurlander, CF Lai, J Tan, CC Chou, CH Geisler, J Schriber, LE Blumenson, SK Narula, H Baumann and MA Caligiuri
Department of Molecular and Cell Biology, Roswell Park Cancer Institute,
Buffalo, NY 14263, USA.
B-cell chronic lymphocytic leukemia (B-CLL) cells accumulate in vivo in the
G0/G1 phase of the cell cycle, suggesting that their malignant expansion is
due, at least in part, to a delay in cell death. However, the cellular or
molecular factors responsible for a delay in B-CLL cell death are unknown.
B-CLL cells do express receptors for interferon- alpha (IFN-alpha) and
IFN-gamma, and activation of both has been shown to promote B-CLL survival
in vitro by preventing apoptosis. The interleukin-10 (IL-10) receptor is
another member of the IFN receptor family, but its ligand, IL-10, has been
reported to induce apoptosis in B-CLL cells. In the current study, we
undertook a biochemical analysis of IL-10 receptor expression on freshly
isolated B-CLL cells and characterized the functional responsiveness of
IL-10 binding to its constitutively expressed receptor. We show that B-CLL
cells bind IL-10 with significant specificity and express between 47 and
127 IL-10 receptor sites per cell, with a dissociation constant in the
range of 168 to 426 x 10(-12) mol/L. Ligand binding and activation of the
IL-10 receptor expressed on B-CLL cells results in the phosphorylation of
signal transducer and activator of transcription 1 (STAT1) and STAT3
proteins. This pattern of STAT protein phosphorylation is identical to
IL-10 receptor activation on normal cells and similar to IFN-alpha (STAT1
and STAT3) and IFN-gamma (STAT1) receptor activation in CLL. Further, in
consecutive samples of fresh blood obtained from patients with B-CLL cells,
the addition of IL-10 inhibited B-CLL proliferation, enhanced B-CLL
differentiation, but did not induce apoptosis. Indeed, IL-10, like
IFN-gamma, was able to significantly reduce the amount of B- CLL cell death
caused by hydrocortisone-induced apoptosis. We conclude that cytokines,
which signal through the interferon family of receptors, have comparable
functional effects on B-CLL cells.
Volume 89,
Issue 11,
pp. 4146-4152,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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