CGS 21680, Dibutyryl Cyclic AMP and Rolipram Attenuate the Pro-inflammatory Interactions of the Pseudomonas aeruginosa -derived Pigment, 1-Hydroxyphenazine, with Human Neutrophils

2000 ◽  
Vol 13 (6) ◽  
pp. 293-299 ◽  
Author(s):  
G. Ramafi ◽  
R. Anderson ◽  
A.J. Theron ◽  
C. Feldman ◽  
G.W. Taylor ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cyclic Amp ◽  
Human Neutrophils ◽  
Dibutyryl Cyclic Amp ◽  
Cgs 21680

scholarly journals MEDIATION OF IMMUNOLOGIC DISCHARGE OF LYSOSOMAL ENZYMES FROM HUMAN NEUTROPHILS BY GUANOSINE 3',5'-MONOPHOSPHATE

1974 ◽  
Vol 140 (1) ◽  
pp. 225-238 ◽  
Author(s):  
L. J. Ignarro ◽  
W. J. George
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Lysosomal Enzymes ◽  
Extracellular Calcium ◽  
Human Neutrophils ◽  
Enzyme Release ◽  
Dibutyryl Cyclic Amp ◽  
Relationship Of ◽  
The Relationship ◽  
Stimulation Of

The purpose of this investigation was to elucidate the relationship of cyclic GMP and calcium to the immunologic discharge of lysosomal enzymes from purified human neutrophils. Contact of neutrophils with a variety of immunologic stimuli, including zymosan particles treated with either normal or rheumatoid arthritic (RA) serum, heat-aggregated (agg) IgG, particulate and immobilized agg IgG each treated with RA serum, and zymosan-treated serum, provoked the discharge of ß-glucuronidase, but not cytoplasmic lactate dehydrogenase, and stimulated the accumulation of cyclic GMP. Both enzyme release and elevation of cyclic GMP levels required the presence of extracellular calcium as neither cellular event proceeded in its absence. Cholinergic enhancement of the immunologic secretion of ß-glucuronidase from neutrophils by acetylcholine was associated with a concomitant accumulation of cyclic GMP. These actions of acetylcholine on neutrophils did not proceed in the absence of extracellular calcium. Whereas the concentrations of cyclic GMP in neutrophils were elevated by both immune reactants and a combination of the latter and acetylcholine, cyclic AMP levels remained unaltered. Thus, cyclic GMP, but not cyclic AMP, was associated with the immunologic and pharmacologic discharge of lysosomal enzymes from neutrophils. Contrariwise, cyclic AMP, but not cyclic GMP, was associated with inhibition of lysosomal enzyme release. For example, dibutyryl cyclic AMP and epinephrine inhibited the release of ß-glucuronidase from neutrophils that was elicited by each of the immune reactants tested. Moreover, cyclic AMP levels in the cells were elevated markedly in every instance that enzyme discharge was inhibited by epinephrine. Epinephrine did not alter the neutrophil concentrations of cyclic GMP at times when those of cyclic AMP were elevated. The data in this report constitute partial evidence that the immunologic discharge of lysosomal enzymes from human neutrophils is mediated or signaled by intracellular cyclic GMP and that calcium is linked to this stimulation of enzyme secretion.

scholarly journals Lipopeptides activate Gi-proteins in dibutyryl cyclic AMP-differentiated HL-60 cells

1993 ◽  
Vol 296 (1) ◽  
pp. 245-251 ◽  
Author(s):  
J F Klinker ◽  
A Höer ◽  
I Schwaner ◽  
S Offermanns ◽  
K Wenzel-Seifert ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Phosphatidic Acid ◽  
G Protein ◽  
Acid Formation ◽  
Human Neutrophils ◽  
Dependent Manner ◽  
Dibutyryl Cyclic Amp ◽  
Gtp Hydrolysis ◽  
Alpha Subunits ◽  
Gi Proteins

Synthetic lipopeptides activate superoxide-anion (O2-) formation in human neutrophils in a pertussis-toxin (PTX)-sensitive manner, suggesting the involvement of G-proteins of the Gi family in the signal-transduction pathway. We compared G-protein activation by lipopeptides and the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) in dibutyryl-cyclic-AMP-differentiated HL-60 cells. The lipopeptide (2S)-2-palmitoylamino-6-palmitoyloxymethyl-7-palmitoyloxy heptanoyl-SK4 (Pam3AhhSK4) and fMLP activated high-affinity GTPase, i.e. the enzymic activity of G-protein alpha-subunits, in HL-60 membranes in a time- and protein-dependent manner, but they had no effect on Mg(2+)-ATPase and Na+/K(+)-ATPase. Pam3AhhSK4 and fMLP increased Vmax. of GTP hydrolysis. Pam3AhhSK4 activated GTP hydrolysis with half-maximal and maximal effects at about 2 microM and 10 microM respectively. Other lipopeptides activated GTP hydrolysis as well. Lipopeptides were less effective than fMLP to activate GTPase. In membranes from PTX-treated cells, the stimulatory effects of lipopeptides and fMLP on GTPase were abolished. In N-ethylmaleimide-treated membranes, the relative stimulatory effect of Pam3AhhSK4 on GTP hydrolysis was enhanced, whereas that of fMLP was diminished. fMLP and Pam3AhhSK4 activated GTPase in an over-additive manner in N-ethylmaleimide-treated membranes. Unlike fMLP, Pam3AhhSK4 did not enhance incorporation of GTP azidoanilide into, and cholera-toxin-catalysed ADP-ribosylation of Gi-protein alpha-subunits in, HL-60 membranes and did not induce rises in cytosolic Ca2+ concentration. Pam3AhhSK4 and fMLP stimulated phosphatidic acid formation in a PTX-sensitive manner. Pam3AhhSK4 itself did not activate O2- formation, but potentiated the stimulatory effects of fMLP. Our data suggest that (i) lipopeptides activate the GTPase of Gi-proteins, (ii) lipopeptides and fMLP activate Gi-proteins differently, (iii) lipopeptides stimulate phospholipase D via Gi-proteins, and (iv) phosphatidic acid formation is not sufficient for activation of O2- formation.

scholarly journals Effect of rolipram and dibutyryl cyclic AMP on resequestration of cytosolic calcium in FMLP-activated human neutrophils

1998 ◽  
Vol 124 (3) ◽  
pp. 547-555 ◽  
Author(s):  
R Anderson ◽  
A Goolam Mahomed ◽  
A J Theron ◽  
G Ramafi ◽  
C Feldman
Keyword(s):  
Cyclic Amp ◽  
Cytosolic Calcium ◽  
Human Neutrophils ◽  
Dibutyryl Cyclic Amp

scholarly journals Lipopeptides are effective stimulators of tyrosine phosphorylation in human myeloid cells

1992 ◽  
Vol 282 (2) ◽  
pp. 551-557 ◽  
Author(s):  
S Offermanns ◽  
R Seifert ◽  
J W Metzger ◽  
G Jung ◽  
A Lieberknecht ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Tyrosine Phosphorylation ◽  
Pertussis Toxin ◽  
Myeloid Cells ◽  
Human Neutrophils ◽  
Dibutyryl Cyclic Amp ◽  
Dihydroxyvitamin D3 ◽  
Peak Response ◽  
1,25 Dihydroxyvitamin D3 ◽  
N Terminus

Synthetic lipopeptide analogues of the N-terminus of bacterial lipoprotein are effective activators of macrophages, neutrophils and lymphocytes. We studied the effect of the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]- (R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine [Pam3Cys-Ser-(Lys)4] on tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells, using anti-phosphotyrosine antibodies. Pam3Cys-Ser-(Lys)4 concentration-dependently stimulated tyrosine phosphorylation of 100/110 kDa and 60 kDa proteins and, to a lesser extent, of 55 kDa and 70/75 kDa proteins. Half-maximal and maximal effects were observed at concentrations of 1-6 and 5-50 micrograms/ml respectively. The lipopeptide-induced increase in phosphorylation was rapid and transient, with a peak response after 30-60 s. The lipopeptide (2S)-2-palmitoylamino-6-palmitoyloxymethyl-7-palmitoyloxy heptanoyl-Ser-(Lys)4 [Pam3Ahh-Ser-(Lys)4] was as potent as Pam3Cys-Ser(Lys)4, whereas (2S,6S)-2-palmitoylamino-6,7-bis(palmitoyloxy)heptanoyl++ +-Ser-(Lys)4 [Pam3Adh-Ser-(Lys)4] and Pam3Cys-Ser-Gly did not induce tyrosine phosphorylation. Lipopeptide-induced tyrosine phosphorylation was not affected by treatment of cells with pertussis toxin. Neither phorbol 12-myristate 13-acetate nor A23187 induced tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells. In HL-60 promyelocytes, Pam3Cys-Ser-(Lys)4 had no effect on tyrosine phosphorylation, whereas the lipopeptide also induced tyrosine phosphorylation in 1,25-dihydroxyvitamin-D3-differentiated HL-60 cells and in human neutrophils. These results show that lipopeptides are effective stimulators of tyrosine phosphorylation in mature human myeloid cells.

Modulation of the respiratory burst in human neutrophils by isoproterenol and dibutyryl cyclic AMP

1993 ◽  
Vol 43 (1-2) ◽  
pp. 59-68 ◽  
Author(s):  
Kimberly L. Gibson-Berry ◽  
John C. Whitin ◽  
Harvey J. Cohen
Keyword(s):  
Cyclic Amp ◽  
Respiratory Burst ◽  
Human Neutrophils ◽  
Dibutyryl Cyclic Amp

The inhibitory effects of some adenosine nucleolipids on the lipolysis in rat epididymal fat pads in vitro

1979 ◽  
Vol 44 (5) ◽  
pp. 1651-1656 ◽  
Author(s):  
Sixtus Hynie ◽  
Jiří Smrt
Keyword(s):  
Fatty Acids ◽  
Cyclic Amp ◽  
Dibutyryl Cyclic Amp ◽  
Inhibitory Effects ◽  
Epididymal Fat ◽  
Fat Pads

3'-Oleolyl-2,3-dihydroxypropyl-AMP, 3'-stearoyl-2,3-dihydroxypropyl-AMP, octadecyl-AMP and palmitamidoethyl-AMP inhibited in comparison with adenosine or fatty acids much stronger the lipolysis in rat epididymal fat pads in vitro stimulated by isoproterenol, theophylline and dibutyryl cyclic AMP. The inhibition of the effects of the two latter drugs suggest that the described effect is caused not only by the inhibition of the cyclic AMP production but also by the inhibition of its effect on the following steps in process of lipolysis.

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