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Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 946-951
Adenosine Triphosphate-Induced Shedding of CD23 and L-Selectin
(CD62L) From Lymphocytes Is Mediated by the Same Receptor but
Different Metalloproteases
B. Gu,
L.J. Bendall, and
J.S. Wiley
From Sydney University Department of Medicine, Nepean Hospital,
Penrith, Australia.
CD23 is a transmembrane protein expressed on the surface of
B-lymphocytes that binds IgE, CD21, CD11b, and CD11c. High
concentrations of soluble CD23 and L-selectin are found in the serum of
patients with B-chronic lymphocytic leukemia (B-CLL). Because
extracellular adenosine triphosphate (ATP) causes shedding of
L-selectin via activation of P2Z/P2X7 receptors expressed
on B-CLL lymphocytes, we studied the effect of ATP on shedding of CD23.
ATP-induced shedding of CD23 at an initial rate of 12% of that for
L-selectin, whereas the EC50 for ATP was identical (35 µmol/L) for shedding of both molecules. Furthermore, benzoylbenzoyl
ATP also produced shedding of CD23 and L-selectin with the same agonist
EC50 values for both (10 µmol/L). Inactivation of the
P2Z/P2X7 receptor by preincubation with oxidized ATP
abolished ATP-induced shedding of both molecules. Moreover, KN-62, the
most potent inhibitor for the P2Z/P2X7 receptor, inhibited
ATP-induced shedding of both CD23 and L-selectin with the same
IC50 (12 nmol/L). Ro 31-9790, a membrane permeant zinc
chelator that inhibits the phorbol-ester-stimulated shedding of
L-selectin, also inhibited shedding of CD23 from B-CLL lymphocytes.
However, the IC50 for this inhibition by Ro31-9790 was
different for L-selectin and CD23 (83 v 6 µmol/L,
respectively). Although L-selectin was completely shed by incubation of
cells with phorbol-ester, CD23 was not lost under these conditions. The
data show that extracellular ATP induces shedding of L-selectin and
CD23 from B-CLL lymphocytes by an action mediated by the
P2Z/P2X7 receptor. However, different membrane
metalloproteases seem to mediate the shedding of L-selectin and CD23.
© 1998 by The American Society of Hematology.
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