Signaling through CD43 induces natural killer cell activation, chemokine release, and PYK-2 activation

Natural killer (NK) cell activation is the result of a balance between posi tive and negative signals triggered by specific membrane receptors. We repo rt here the activation of NK cells induced through the transmembrane glycop rotein CD43 (leukosialin, sialophorin). Engagement of CD43 by specific anti bodies stimulated the secretion of the chemokines RANTES, macrophage inflam matory protein (MIP)-1 alpha, and MIP-1 beta, which was prevented by treatm ent of cells with the specific tyrosine kinase inhibitor genistein. Further more, signaling through CD43 increased the cytotoxic activity of NK cells a nd stimulated an increase in the tyrosine kinase activity in antiphosphotyr osine immune complexes of NK cell lysates. PYK-2 was identified among the t yrosine kinase proteins that become activated. Hence, PYK-5 activation was observed after 20 minutes of CD43 stimulation, reached a maximum after 45 t o 60 minutes, and decreased to almost basal levels after 120 minutes of tre atment. Together, these results demonstrate the role of CD43 as an activati on molecule able to transduce positive activation signals in NK cells, incl uding the regulation of chemokine synthesis, killing activity, and tyrosine kinase activation. (C) 1999 by The American Society of Hematology.