CGS 21680, dibutyryl cyclic AMP and rolipram attenuate the pro-inflammatory interactions of the Pseudomonas aeruginosa -derived pigment, 1-hydroxyphenazine, with human neutrophils.
The effects of the intracellular adenosine 3':5' cyclic monophosphate (cAMP)-elevating agents, CGS 21680 (0.01- 1 microM) and rolipram (0.01-1 microM), as well as those of dibutyryl cAMP (0. 05-4 mM) on the pro-inflammatory interactions of the P. aeruginosa -derived pigment, 1-hydroxyphenazine (1-hp, 3.1 and 12.5 microM), with human neutrophils have been investigated in vitro. Ca(2+)fluxes in FMLP-activated neutrophils were measured using a fura-2/AM spectrofluorimetric procedure, while a colourimetric method was used to measure release of the primary granule enzyme, elastase, from the cells. Treatment with 1-hp resulted in delayed clearance of Ca(2+)from the cytosol of N -formyl- L -methionyl- L -leucyl- L -phenylalanine (FMLP, 1 microM)-activated neutrophils and increased release of elastase. All 3 test agents caused dose-related antagonism of 1-hp-mediated potentiation of elastase release from activated neutrophils, which was associated with restoration of Ca(2+)homeostasis. These observations demonstrate the potential of cAMP-elevating agents, acting on Ca(2+)clearance mechanisms in activated neutrophils, to attenuate the potentially harmful pro-inflammatory effects of 1-hp.
Ramafi
G
G
MRC Unit for Inflammation and Immunity, University of Pretoria, Pretoria, South Africa.
Anderson
R
R
Theron
A J
AJ
Feldman
C
C
Taylor
G W
GW
Wilson
R
R
Cole
P J
PJ
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003994:Bucladesine / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010619:Phenazines / Q000378:metabolism*; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa; D020889:Rolipram / Q000008:administration & dosage / Q000494:pharmacology*
D000959:Antihypertensive Agents; D015220:Calcium Channels; D010619:Phenazines; D010627:Phenethylamines; D010726:Phosphodiesterase Inhibitors; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C050093:1-hydroxyphenazine; D003994:Bucladesine; D020889:Rolipram; D000241:Adenosine; D002118:Calcium