title: Anti-apoptotic mechanism and reduced expression of phospholipase D in spontaneous and Fas-stimulated apoptosis of human neutrophils.
abstract: Neutrophil apoptosis is a constitutive process that can be enhanced or delayed by signals triggered by various stimuli. In this work, we investigated the action mechanism of phospholipase D (PLD) and its expression in the inhibition of spontaneous and Fas-mediated apoptosis. Anti-Fas antibody-stimulated apoptosis of neutrophils was significantly blocked by the exogenous addition of bacterial PLD from Streptomyces chromofuscus (scPLD), and neutrophils cultured for 24 h in the presence of anti-Fas antibody showed lower agonist-stimulated PLD activity compared to untreated cells. The amount of PLD1a protein reduced time-dependently in cultured neutrophils, but was recovered by treating with LPS or GM-CSF. The reduction in PLD1a protein level was blocked by caspase inhibitors. The exogenous addition of scPLD blocked the up-regulation of Fas-associated death domain expression, mitochondrial permeability, and the cleavages of procaspase-8, procaspase-3, and protein kinase C-delta. We also found that the protein level of apoptosis-inducing factor was increased in cultured neutrophils but its expression was reduced by scPLD. However, sulfasalazine-induced apoptosis and change of protein expression were not blocked by scPLD. Taken together, the activity and protein levels of PLD play a role as an anti-apoptotic factor by acting at multiple levels of the apoptotic cascade in neutrophils.
authors.affiliation: Medical Research Center for Cancer Molecular Therapy, Dong-A University, Busan, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Oh
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Jang
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Ja-Woong
authors.initials: JW
authors.lastname: Kim
authors.forename: Do Sik
authors.initials: DS
authors.lastname: Min
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Kwak
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051033:Apoptosis Inducing Factor; D015153:Blotting, Western; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D056970:Co-Repressor Proteins; D004305:Dose-Response Relationship, Drug; D005420:Flavoproteins / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D018832:Molecular Chaperones; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D005420:Flavoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D019014:fas Receptor; D010739:Phospholipase D; D020169:Caspases