2-chloroadenosine stimulates granule exocytosis from mouse natural killer cells: evidence for signal transduction through a novel extracellular receptor

Experimental Cell Research
B A WilliamsDavid W Hoskin

Abstract

The effect of 2-chloroadenosine (2CA), an adenosine receptor agonist, on the activation status of mouse natural killer (NK) cells was determined. Splenic lymphocytes incubated with 2CA exocytosed an NK cell-associated granzyme with N alpha-CBZ-L-lysine thiobenzyl ester (BLT) esterase activity in a dose- and time-dependent manner. Selective depletion of NK cells by anti-asialoGM1 antibody plus complement pretreatment confirmed that NK cells were the source of the BLT esterase activity. 2CA-induced granule exocytosis was not reduced in the presence of the nucleoside uptake blockers NBTI, dilazep, or dipyridamole, indicating the involvement of an extracellular receptor. However, adenosine or other A1, A2, or A3 cell-surface adenosine receptor agonists failed to trigger the exocytotic process. Furthermore, the nonselective adenosine receptor antagonist theophylline, as well as the selective A1 receptor antagonist DPCPX and the selective A2 receptor antagonist DMPX, did not interfere with 2CA-induced BLT esterase secretion. These data suggest that 2CA acts on NK cells via a novel (non-A1/A2/A3) cell-surface receptor. Genistein, a protein tyrosine kinase inhibitor, and calphostin C, a protein kinase C inhibitor, both interfered with ...Continue Reading

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Citations

Dec 2, 2009·Modern Rheumatology·Edwin S L Chan, Bruce N Cronstein
Jul 16, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Balázs CsókaGyörgy Haskó
Dec 28, 2007·Journal of Leukocyte Biology·György Haskó, Pál Pacher
Sep 4, 2015·Immunology·Felipe Flores-SantibáñezDaniela Sauma
Nov 15, 2013·Nature Reviews. Cancer·Luca AntonioliGyörgy Haskó

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