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Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2767-2777
Signaling Through CD43 Induces Natural Killer Cell
Activation, Chemokine Release, and PYK-2 Activation
Marta Nieto,
José Luis Rodríguez-Fernández,
Francisco Navarro,
David Sancho,
José M.R. Frade,
Mario Mellado,
Carlos Martínez-A,
Carlos Cabañas, and
Francisco Sánchez-Madrid
From the Servicio de Inmunología, Hospital de la Princesa,
Universidad Autónoma de Madrid, Madrid, Spain; the Departamento
de Bioquímica y Biología Molecular, Facultad de
Medicina, Universidad Complutense, Madrid, Spain; and the Department of
Immunology and Oncology, Centro Nacional de Biotecnología,
CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco,
Madrid, Spain.
Natural killer (NK) cell activation is the result of a balance
between positive and negative signals triggered by specific membrane
receptors. We report here the activation of NK cells induced through
the transmembrane glycoprotein CD43 (leukosialin, sialophorin).
Engagement of CD43 by specific antibodies stimulated the secretion of
the chemokines RANTES, macrophage inflammatory protein
(MIP)-1 , and MIP-1 , which was prevented by treatment of cells with the specific tyrosine kinase inhibitor genistein. Furthermore, signaling through CD43 increased the cytotoxic activity of
NK cells and stimulated an increase in the tyrosine kinase activity in
antiphosphotyrosine immune complexes of NK cell lysates. PYK-2 was
identified among the tyrosine kinase proteins that become activated.
Hence, PYK-2 activation was observed after 20 minutes of CD43
stimulation, reached a maximum after 45 to 60 minutes, and decreased to
almost basal levels after 120 minutes of treatment. Together, these
results demonstrate the role of CD43 as an activation molecule able to
transduce positive activation signals in NK cells, including the
regulation of chemokine synthesis, killing activity, and tyrosine
kinase activation.
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