To investigate the role of phospholipases during the activation and priming of neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by peritoneal dialysis effluent (PDE).
Design
Examine the action of 4-hour dwell PDE upon phospholipase activation in the circulating neutrophils obtained from healthy individuals.
Results
We have previously reported that PDE stimulated superoxide release by the NADPH oxidase of human neutrophils and primed the response to the bacterial peptide, fMLP (fMetLeuPhe). To elucidate the biochemical mechanisms underlying these observations, we have examined the roles of phospholipases (PL) C, D, and A2, whose activation causes the release of a range of intracellular secondary messengers. Following fMLP stimulation, we observed a rapid activation of both PLC and PLD as well as a small but nonsignificant increase in PLA2 activity. Peritoneal dialysis effluent alone failed to stimulate either PLC or PLD, while pre-incubation with PDE had no affect upon fMLP-induced PLC and PLD activation. However, PDE caused a small but nonsignificant increase in PLA2 activity (which was comparable to that observed with fMLP) and primed the fMLP-induced response. In common with a role for PLA2 and the subsequent release of arachidonic acid (AA), we have demonstrated dose-dependent inhibition of PDE-induced superoxide release by the PLA2 inhibitor mepacrine, as well as activation and priming of the fMLP-induced superoxide generation by AA.
Conclusions
These results imply that PDE-induced NADPH-oxidase activation and priming in human neutrophils is mediated via a PLA2-dependent but PLC and PLD-independent mechanism.
HarveyD.M., SheppardK., MorganA.G., FletcherJ.Effect of dialysis fluids on phagocytosis and killing by normal neutrophils.J Clin Microbiol1987; 25: 1424–7.
2.
DanielsI., LindsayM.A., PorterC., HaynesA.P., FletcherJ., MorganA.G.Effect of peritoneal dialysis effluent upon superoxide anion production by polymorphonuclear neutrophils.Nephron1993; 64: 382–7.
3.
DanielsI., CrouchS.P.M., LindsayM.A.Primary and secondary granule release by polymorphonuclear leukocytes exposed to peritoneal dialysis effluent.Clin Diagn Lab Immunol1994; 1: 227–31.
4.
CockcroftS.G-protein-regulated phospholipase C, D and A2-mediated signalling in neutrophils.Biochim Biophys Acta1992; 1113: 135–60.
5.
BokochG.M.Chemoattractant signaling and leukocyte activation.Blood1995; 86: 1649–60.
6.
BillahM.M., EckelS., MullmanT J., EganR.W., SiegelM.I.Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophil. Involvement of phosphatidate phosphohydrolase in signal transduction.J Biol Chem1989; 264: 17069–77.
7.
LamB.K., WongpyPhospholipase A2 (PLA2) release leukotrienes and other lipoxygenase products from endogenous sources.Adv Prostaglandin Thromboxane Leukot Res1989; 19:598–601.
8.
GrynkiewiczG., PoenieM., TsienR.A new generation of Ca2+ indicators with greatly improved fluorescence properties.J Biol Chem1985; 260: 3440–50.
9.
GyllenhammerH.Lucigenin enhanced chemilumines cence, the assessment of neutrophil superoxide anion production.J Immunol Methods1987; 97: 209–13.
10.
BlighE.G., DyerW.J.A rapid method of total lipid extraction and purification.Can J Biochem Physiol1959; 37: 911–19.
11.
PreissJ., LoomisC.R., BishopW.R., SteinR., NiedelJ.E., BellR.M.Quantitative measurement of sn-l, 2 diacylglycerols present in platelets, hepatocytes and ras and sis transformed normal rat kidney cells.J Biol Chem1986; 261: 8597–600.
12.
CockcroftS., StutchfieldJ.The receptors for ATP and fMetLeuPhe are independently coupled to phospholipase C and A2 via G-proteins.Biochem J1989; 263: 715–23.
13.
BauldryS.A., BassD.A., CousartS.L., McCa11C.E.Tumor necrosis factor-α priming of phospholipase D in human neutrophils. Correlation between phosphatidic acid production and superoxide generation.J Biol Chem1991; 266: 4174–5.
14.
DanaR., MalechH.L., LevyR.The requirement for phospholipase A2 for activation of the assembled NADPH oxidase in human neutrophils.Biochem J1994; 297: 217–23.
15.
HendersonL.M., ChappellJ.B., JonesO.T.G.Superoxide generation is inhibited by phospholipase A2 inhibitors. The role of phospholipase A2 in the activation of the NADPH oxidase.Biochem J1989; 264: 249–55.
16.
JacobsonP.J., SchrierD.J.Regulation of CD11b/CD18 expression in human neutrophils by phospholipase A2.JImmunol1993; 151: 5639–52.
17.
DoerflerM.E., WeissJ., ClarkJ.D., ElsbachP.Bacterial lipopolysaccharide primes human neutrophils for enhanced release of arachidonic acid and causes phosphorylation of an 85-kD cytosolic phospholipase A2.J Clin Invest1994; 93: 1583–91.
18.
BauldryS.A., McCa11C.E., CousartS.L., BassD.A.Tumor necrosis factor-α priming of phospholipase A2 activation in human neutrophils.J Biol Chem1991; 146: 1277–85.
19.
BadweyJ.A., CurnetteJ.T., RobinsonJ.M., BerdeC.B., KarnovskyM.J., KarnovskyM.L.Effects of free fatty acids on release of superoxide and on change of shape by human neutrophils.J Biol Chem1984; 259: 7870–7.
20.
CurnetteJ.T., BadweyJ.A., RobinsonJ.M., KarnovskyM.J., KarnovskyM.L.Studies on the mechanism of superoxide release from human neutrophils stimulated with arachidonate.J Biol Chem1984; 259: 11851–7.
21.
AebischerC.P., PascheI., JorgA.Nanomolar arachidonic acid influences the respiratory burst in eosinophils and neutrophils induced by GTP-binding protein. A comparative study of the respiratory burst in bovine eosinophils and neutrophils.Eur J Biochem1993; 218: 669–77.
22.
HendersonL.M., MotileS.K., ChappellJ.B.The immediate activator of the NADPH oxidase is arachidonate not phosphorylation.Eur J Biochem1993; 211: 157–62.
23.
CosteiloJ., FransonR.C., LandwehrK., LandwehrD.M.Activity of PLA2 in plasma increases in uraemia.Clin Chem1990; 36: 198–200.
24.
FransonR., DobrowR., WeissJ., ElsbachP., WeglickiW.B.Isolation and characterization of a PLA2 from an inflammatory exudate.J Lipid Res1978; 19: 18–24.
25.
PruzankiW., SaitoS., StafanskiE., VadasP.Comparison of group I and II soluble PLA2 activities on phagocytic functions of human PMN and mononuclear phagocytes.Inflammation1991; 15: 127–35.
26.
HomayounP., StaceyD.W.Inhibitory effect of arachidonic acid on GTPase activating protein is antagonized by 1-stearoyl, 2-arachidonoyl glycerol.Biochem Biophys Res Commun1993; 194: 1413–19.
27.
SermonB.A., EcclestonJ.F., SkinnerR.H., LoweP.N.Mechanism of inhibition by arachidonic acid of the catalytic activity of ras GTPase-activating proteins.J Biol Chem1996; 271: 1566–72.
28.
KhanW.A., BlobeG.C., HannunY.A.Arachidonic acid and free fatty acids as secondary messengers and the role of protein kinase C.Cell Signal1995; 7: 171–84.
29.
RaoG.N., BaasA.S., GlasgowW.C., ElingT.E., RungeM.S., AlexanderR.W.Activation of mitogen-activated protein kinases by arachidonic acid and its metabolites in vascular smooth muscle cells.J Biol Chem1994; 269: 32586–91.
30.
HiiC.S.T., FerranteA., EdwardsY.S.Activation of mitogen-activatecl protein kinase by arachidonic acid in rat liver epithelial WB cells by protein kinase Cdependent mechanism.J Biol Chem1995; 270: 4201–4.
31.
SawaiT., AsadaM., NtinoiH.Combination of arachidonic acid and guanosine 5′-O-(3-thiotriphosphate) induce translocation of rac p21s to membrane and activation of NADPH oxidase in a cell-free system.Biochem Biophys Res Commun1993; 195: 264–9.
32.
LynnW.A., RaetzC.R.H., QureshiN., GolenbockD.T.Lipopolysaccharide-indticed stimulation of CD11b/ CD18 expression on netitrophils. Evidence of specific receptor-based response and inhibition by lipid Abased antagonists.JImmunol1991; 147: 3072–9.
33.
KlebanoffS.J., VaclasM.A., HarlanJ.M.Stimulation of neutrophils by TNFα.J Immunol1986; 136: 4220–5.
34.
GtithrieL.A., McPhailL.C., HensonP.M., JohnstonR.B.Jr.Priming of neutrophils for enhanced release of oxygen metabolites by bacterial lipopolysaccharide. Evidence for increased activity of the superoxide-producing enzyme.JExp Med1984; 160: 1656–71.
35.
JosephC.K., WrightS.D., BornmannW.G.Bacterial lipopolysaccharide has structural similarity to ceramide and stimulates ceramide-activated protein kinase in myeloid cells.J Biol Chem1994; 269: 17606–10.
36.
KolesnickR., GoldeD.W.The sphingomyelin pathway in tumor necrosis factor and interleukin-l signalling.Cell1994; 77: 325–8.
37.
WeinsteinS.L., GoldM.R., DeFrancoA.L.Bacteriallipo-polysaccharide stimulates protein tyrosine phosphorylation in macrophages.Proc Natl Acad Sci USA1991; 88: 4148–52.
38.
RheeM.S., McGoldrickM.D., MeuwissenH.J.Serum factors from patients with chronic renal failure enhance PMN oxidative metabolism.Nephron1986; 42: 6–13.
39.
VanholderR., DeSmetR., WaterloosM.A.Mechanisms of ureamic inhibition of phagocytic reactive species production: characterization of the role of pcresol.Kidney Int1995; 9: 510–17.
40.
Haag-WeberM., MaiB., CohenG., HorlW.H.GIP and DIP: a new view of uraemic toxicity.Nephrol Dial Transplant1994; 9: 346–7.
41.
PorterC.J., BurdenR.P., MorganA.G., DanielsI., FletcherJ.Impaired polymorphonuclear neutrophil function in end stage renal failure and its correction by continuous ambulatory peritoneal dialysis.Nephron1995; 71: 133–7.
