Anti-apoptotic mechanism and reduced expression of phospholipase D in spontaneous and Fas-stimulated apoptosis of human neutrophils

Sun Young Lee, Ji Young Oh, Min Jung Lee, Min Jung Jang, Hae Young Park, Ja Woong Kim, Do Sik Min, Yeong Min Park, Young Chae Chang, Yoe Sik Bae, Jong Young Kwak

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13 Citations (Scopus)

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 is 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 PLD1 a 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-δ. 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.

Original languageEnglish
Pages (from-to)2760-2770
Number of pages11
JournalEuropean Journal of Immunology
Volume34
Issue number10
DOIs
Publication statusPublished - 2004 Oct

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Lee, S. Y., Oh, J. Y., Lee, M. J., Jang, M. J., Park, H. Y., Kim, J. W., Min, D. S., Park, Y. M., Chang, Y. C., Bae, Y. S., & Kwak, J. Y. (2004). Anti-apoptotic mechanism and reduced expression of phospholipase D in spontaneous and Fas-stimulated apoptosis of human neutrophils. European Journal of Immunology, 34(10), 2760-2770. https://doi.org/10.1002/eji.200425117