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

Abstract:

: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)-1alpha, and MIP-1beta, 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.

journal_name

Blood

journal_title

Blood

authors

Nieto M,Rodríguez-Fernández JL,Navarro F,Sancho D,Frade JM,Mellado M,Martínez-A C,Cabañas C,Sánchez-Madrid F

subject

Has Abstract

pub_date

1999-10-15 00:00:00

pages

2767-77

issue

8

eissn

0006-4971

issn

1528-0020

journal_volume

94

pub_type

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