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p55 and p75 tumor necrosis factor receptors in patients with chronic
lymphocytic leukemia
A Waage, N Liabakk, E Lien, J Lamvik and T Espevik
Department of Medicine, University of Trondheim, Norway.
We studied the expression of the two tumor necrosis factor (TNF) receptors,
p55 and p75, on B cells from patients with chronic lymphocytic leukemia
(CLL), and the presence of soluble TNF receptors in serum. Expression of
membrane-associated receptors was quantified by double labeling of
peripheral blood mononuclear cells (PBMC) with monoclonal antibodies
against CD19 and p55/p75 TNF receptors and flow cytometry. A high fraction
of the CD19+ cells expressed the p55 receptor (44% +/- 34% [SD]) and p75
receptor (61% +/- 31%). In healthy controls, 0% to 1% of the CD19+ cells
expressed the p55 receptor and 0% to 10% expressed the p75 receptor.
Incubation of CD19+ cells with 10 ng/mL of TNF increased the incorporation
of thymidine in 11 patients tested, and this was decreased to 65% (P <
.05) by antibodies to the p55 receptor or the p75 receptor, and to 35% +/-
7% (P < .001) when both antibodies were combined. With an enzyme-linked
immunoassay, we measured soluble TNF receptors in serum from CLL patients.
The mean level of p55 receptors was increased to 12.9 +/- 8.9 ng/mL (P <
.000001 v normal). The mean level of p75 receptors was increased to 13 +/-
24 ng/mL (P = .01 v normal). The membrane expression of the two receptors
was positively correlated (r +/- 97, P < .01); however, there was no
correlation between membrane expression and serum concentration of either
receptor. Autologous serum containing high levels of soluble TNF receptors
inhibited TNF-induced proliferation of CD19+ cells. In conclusion, we have
demonstrated that neoplastic cells from patients with CLL have increased
expression of p55 and p75 TNF receptors, and that both receptors mediate
signal to proliferation. Furthermore, serum from CLL patients has elevated
levels of soluble TNF receptors, which may counteract the proliferative
effect of TNF.
Volume 80,
Issue 10,
pp. 2577-2583,
11/15/1992
Copyright © 1992 by The American Society of Hematology
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