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The role of membrane lipids in the induction of macrophage apoptosis by microparticles.

Publication ,  Journal Article
Huber, LC; Jüngel, A; Distler, JHW; Moritz, F; Gay, RE; Michel, BA; Pisetsky, DS; Gay, S; Distler, O
Published in: Apoptosis
February 2007

Microparticles are membrane-derived vesicles that are released from cells during activation or cell death. These particles can serve as mediators of intercellular cross-talk and induce a variety of cellular responses. Previous studies have shown that macrophages undergo apoptosis after phagocytosing microparticles. Here, we have addressed the hypothesis that microparticles trigger this process via lipid pathways. In these experiments, microparticles induced apoptosis in primary macrophage cells or cell lines (RAW 264.7 or U937) with up to a 5-fold increase. Preincubation of macrophages with phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)BP) reduced the microparticle-induced apoptosis in a dose-dependent manner. PtdIns(3,5)BP is a specific inhibitor of the acid sphingomyelinase and thus can block the generation of pro-apoptotic ceramides. Similarly, the pre-incubation of macrophages with PtdIns(3,5)BP prevented microparticle-induced upregulation of caspase 8, which is a major target molecule of ceramide action in the apoptosis pathway. PtdIns(3,5)BP, however, had no effect on the spontaneous rate of apoptosis. To evaluate further signaling pathways induced by microparticles, the extracellular signal regulated kinase (ERK-) 1 was investigated. This kinase plays a role in activating phospholipases A2 which cleaves membrane phospholipids into arachidonic acid; microparticles have been suggested to be a preferred substrate for phospholipases A2. As shown in our experiments, microparticles strongly increased the amount of phosphorylated ERK1/2 in RAW 264.7 macrophages in a time-dependent manner, peaking 15 min after co-incubation. Addition of PD98059, a specific inhibitor of ERK1, prevented the increase in apoptosis of RAW 264.7 macrophages. Together, these data suggest that microparticles perturb lipid homeostasis of macrophages and thereby induce apoptosis. These results emphasize the importance of biolipids in the cellular cross-talk of immune cells. Based on the fact that in clinical situations with excessive cell death such as malignancies, autoimmune diseases and following chemotherapies high levels of circulating microparticles might modulate phagocytosing cells, a suppression of the immune response might occur due to loss of macrophages.

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Published In

Apoptosis

DOI

ISSN

1360-8185

Publication Date

February 2007

Volume

12

Issue

2

Start / End Page

363 / 374

Location

Netherlands

Related Subject Headings

  • Up-Regulation
  • U937 Cells
  • Sphingomyelin Phosphodiesterase
  • Phosphatidylinositol Phosphates
  • Models, Biological
  • Mitogen-Activated Protein Kinases
  • Mice
  • Membrane Lipids
  • Macrophages
  • Jurkat Cells
 

Citation

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Huber, L. C., Jüngel, A., Distler, J. H. W., Moritz, F., Gay, R. E., Michel, B. A., … Distler, O. (2007). The role of membrane lipids in the induction of macrophage apoptosis by microparticles. Apoptosis, 12(2), 363–374. https://doi.org/10.1007/s10495-006-0622-7
Huber, Lars C., Astrid Jüngel, Jörg H. W. Distler, Falk Moritz, Renate E. Gay, Beat A. Michel, David S. Pisetsky, Steffen Gay, and Oliver Distler. “The role of membrane lipids in the induction of macrophage apoptosis by microparticles.Apoptosis 12, no. 2 (February 2007): 363–74. https://doi.org/10.1007/s10495-006-0622-7.
Huber LC, Jüngel A, Distler JHW, Moritz F, Gay RE, Michel BA, et al. The role of membrane lipids in the induction of macrophage apoptosis by microparticles. Apoptosis. 2007 Feb;12(2):363–74.
Huber, Lars C., et al. “The role of membrane lipids in the induction of macrophage apoptosis by microparticles.Apoptosis, vol. 12, no. 2, Feb. 2007, pp. 363–74. Pubmed, doi:10.1007/s10495-006-0622-7.
Huber LC, Jüngel A, Distler JHW, Moritz F, Gay RE, Michel BA, Pisetsky DS, Gay S, Distler O. The role of membrane lipids in the induction of macrophage apoptosis by microparticles. Apoptosis. 2007 Feb;12(2):363–374.
Journal cover image

Published In

Apoptosis

DOI

ISSN

1360-8185

Publication Date

February 2007

Volume

12

Issue

2

Start / End Page

363 / 374

Location

Netherlands

Related Subject Headings

  • Up-Regulation
  • U937 Cells
  • Sphingomyelin Phosphodiesterase
  • Phosphatidylinositol Phosphates
  • Models, Biological
  • Mitogen-Activated Protein Kinases
  • Mice
  • Membrane Lipids
  • Macrophages
  • Jurkat Cells