Endogenous and exogenous adenosine inhibit granulocyte aggregation without
altering the associated rise in intracellular calcium concentration
KM Skubitz, NW Wickham and DE Hammerschmidt
Department of Medicine, University of Minnesota Medical School,
Minneapolis.
The effects of adenosine, adenosine deaminase (ADA), and an irreversible
ADA inhibitor 2'-deoxycoformycin (DCF) on granulocyte aggregation in
response to four different stimuli: the synthetic chemotaxin
N-formyl-met-leu-phe (FMLP), zymosan-activated plasma (ZAP), the calcium
ionophore A23187, and phorbol myristate acetate (PMA) were studied.
Adenosine inhibited granulocyte aggregation in response to 10(- 7) mol/L
FMLP in a dose-dependent fashion; inhibition in the presence of 1 mumol/L
adenosine was 25% +/- 3% (SD) and was 50% (the maximal inhibition observed)
with 1 mmol/L adenosine. Quantitatively similar results were obtained when
ZAP or A23187 was used as the aggregant but the response to PMA was not
affected. ADA not only reversed the inhibition due to adenosine but
actually augmented the aggregation to FMLP by 118% +/- 9%. Similar results
were obtained with ZAP and A23187 but not with PMA. These effects of ADA
depended on its enzymatic activity as they could be blocked by
preincubation with DCF. Fluorescent measurement of intracellular calcium in
fura-2 loaded granulocyte suspensions established that neither adenosine
nor ADA affected subsequent FMLP-stimulated calcium responses. Adenosine,
therefore, may inhibit granulocyte responsiveness by blocking signal
transduction at a point after calcium entry/mobilization but before
activation of protein kinase C. Furthermore, the augmentation of responses
seen with ADA suggests that endogenous adenosine may be a physiologic
autocrine regulator of granulocyte function.
Volume 72,
Issue 1,
pp. 29-33,
07/01/1988
Copyright © 1988 by The American Society of Hematology
