ADENOSINE TRIPHOSPHATE-INDUCED SHEDDING OF CD23 AND L-SELECTIN (CD62L) FROM LYMPHOCYTES IS MEDIATED BY THE SAME RECEPTOR BUT DIFFERENT METALLOPROTEASES

CD23 is a transmembrane protein expressed on the surface of B-lymphocy tes that binds IgE, CD21, CD11b, and CD11c. High concentrations of sol uble CD23 and L-selectin are found in the serum of patients with B-chr onic lymphocytic leukemia (B-CLL), Because extracellular adenosine tri phosphate (ATP) causes shedding of L-selectin via activation of P2Z/P2 X(7) receptors expressed on B-CLL lymphocytes, we studied the effect o f 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 ident ical (35 mu mol/L) for shedding of both molecules. Furthermore, benzoy lbenzoyl ATP also produced shedding of CD23 and L-selectin with the sa me agonist EC50 values for both (10 mu mol/L). inactivation of the P2Z /P2X(7) receptor by preincubation with oxidized ATP abolished ATP-indu ced shedding of both molecules, Moreover, KN-62, the most potent inhib itor for the P2Z/P2X(7) receptor, inhibited ATP-induced shedding of bo th CD23 and L-selectin with the same IC50 (12 nmol/L). Ro 31-9790, a m embrane permeant zinc chelator that inhibits the phorbolester-stimulat ed shedding of L-selectin, also inhibited shedding of CD23 from B-CLL lymphocytes. However, the IC50 for this inhibition by Ro31-9790 was di fferent for L-selectin and CD23 (83 v 6 mu mol/L, respectively). Altho ugh L-selectin was completely shed by incubation of cells with phorbol -ester, CD23 was not lost under these conditions. The data show that e xtracellular ATP induces shedding of L-selectin and CD23 from B-CLL ly mphocytes by an action mediated by the P2Z/P2X7 receptor. However, dif ferent membrane metalloproteases seem to mediate the shedding of L-sel ectin and CD23. (C) 1998 by The American Society of Hematology.