Adenosine has both pro- and anti-inflammatory effects on neutrophils.
Exposure of cultured neutrophils to 2-chloroadenosine or 5'-N-ethylcar
boxamidoadenosine (NECA) decreased apoptosis after 16 h, with half-max
imal responses for NECA and 2-chloroadenosine of 7.1 +/- 7.7 and 59.0
+/- 32.0 nM, respectively. Adenosine receptor agonists exhibited a ran
k order of potency for decreasing apoptosis of thyl)phenethylamino-5'-
N-ethylcarboxamidoadenosine (CCS 21680) > NECA greater than or equal t
o 2-chloro-N-6-cyclopentyladenosine >> -N-6-(3-iodobenzyl)adenosine-5'
-N-methyluronamide, which is consistent with the affinity order profil
e established for human A(2a) receptors. The reduction in apoptosis in
cultured neutrophils at 16 h by CCS 21680 was due to a delay in apopt
osis, The addition of CGS 21680 (100 nM) increased the half-life for t
he appearance of apoptosis from 10.9 +/- 3.1 to 21.0 +/- 1.0 h. Additi
on of the non-xanthine phosphodiesterase inhibitor 4-(3-butoxy-4-metho
xybenzyl)-2-imidazalidinone (Ro-20-1724; 1 mu M) enhanced the effects
of CGS 21680 at all agonist concentrations, PGE(1) (10 mu M), PGE(2) (
0.1-10 mu M), and dibutyryl cAMP (5-500 mu M) all decreased apoptosis
in cultured neutrophils. The enhancement of the effect of adenosine by
a phosphodiesterase inhibitor and the similar actions of PGE(1), PGE(
1), and dibutyryl cAMP suggest that this decrease in apoptosis may be
mediated by a cAMP-dependent pathway.