The CD14+/lowCD16+ monocyte subset is more susceptible to spontaneous and oxidant-induced apoptosis than the CD14+CD16-subset

C. Zhao, Y. C. Tan, W. C. Wong, X. Sem, H. Zhang, H. Han, S. M. Ong, K. L. Wong, W. H. Yeap, S. K. Sze, P. Kourilsky, S. C. Wong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Human monocytes can be classified into two subsets with distinctive characteristics. In this study, we report a difference in apoptotic potential between these two subsets with CD14+/lowCD16+ monocytes being more susceptible than CD14+CD16+ monocytes to undergo spontaneous apoptosis and apoptosis induced by reactive oxygen species (ROS). By global transcriptomic and proteomic approaches, we observed that CD14+/lowCD16+ monocytes expressed higher levels of pro-apoptotic genes and proteins such as TNFα, caspase 3, Bax and cytochrome c and showed more caspases 3 and 7 activities. They also exhibited greater aerobic respiration resulting in a higher production of ROS from the mitochondria. CD14βCD16+ monocytes, in contrast, showed higher expression of glutathione (GSH)-metabolizing genes such as GSH peroxidase and microsomal GSH S-transferase and were more resistant to oxidative stress than CD14 +/lowCD16β monocytes. The apoptosis of CD14 +/lowCD16β monocytes was ROS dependent as reducing ROS levels significantly reduced cell death. This is the first report of a differential apoptotic propensity of human monocyte subsets, and gaining a better understanding of this process may help to provide a better understanding of the roles of these subsets during homeostasis and under pathological conditions, particularly in situations in which high levels of oxidants are present.

Original languageEnglish (US)
Article numbere95
JournalCell Death and Disease
Volume1
Issue number11
DOIs
StatePublished - Nov 2010

Bibliographical note

Funding Information:
Acknowledgements. We thank Health Sciences Authority (HSA), Singapore, for the supply of buffy coats, the staff of Flow Cytometry and Microarray Units in the Biopolis Shared Facilities, ASTAR for their assistance in cell sorting and samples processing. We also thank Dr. Katja Fink, Dr. Victor Yu and Dr. Han-Kiat Ho for providing reagents and protocols, Dr. Florent Ginhoux, Professor Catharina Svanborg, Dr. Lisa Ng and members of P Kourilsky Laboratory for helpful discussion and critical reading of the manuscript. This research is funded by the Biomedical Research Council, ASTAR, Singapore.

Keywords

  • Anti-oxidation
  • Apoptosis
  • Monocyte subsets
  • Proteomics
  • Reactive oxygen species
  • Transcriptomics

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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