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

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. CD14+CD16− 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+/lowCD16+ monocytes. The apoptosis of CD14+/lowCD16+ 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.

Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets

“…These show that the nonclassical subset is the most mature subset, as cell-cycle withdrawal is normally associated with highly differentiated cells. 28 The results of this analysis were consistent with previous studies, which show that the CD16 ϩ monocytes were proapoptotic 29 and that CD16 ϩ monocytes are more mature. 19,30 The 3 monocytes subsets are defined by different transcriptional profiles…”

Transcription and enhancer profiling in human monocyte subsets

“…Our findings are in line with a previous publication demonstrating an increased mitochondrial activity in CD16 1 monocytes (including nonclassical and intermediate monocytes). 50 The same study also noted a higher susceptibility toward apoptosis induced by reactive oxygen species, which correlated with lower expression of glutathione (GSH)-metabolizing genes such as GSH peroxidase (GSP1) and microsomal GSH S-transferase (MGST1), 50 2 oxidative damagelimiting genes that also show weaker CAGE signals in nonclassical monocytes in the present study.…”

Distinct contribution of protein kinase Cδ and protein kinase Cε in the lifespan and immune response of human blood monocyte subpopulations

“…Our previous work showed that a complex network of survival and apoptotic factors controls the dynamic behaviour of monocyte lifespan . Furthermore, timely activation of apoptosis in monocytes is controlled by negative and positive regulators . We found that caspase‐3, a member of the conserved cysteine‐aspartate‐specific proteases, is essential for monocyte apoptosis .…”

“…Yet, our understanding of the monocyte function and lifespan is mainly based on the knowledge of CD16 − monocytes. Differences in oxidant‐induced apoptosis and glucocorticoid‐induced apoptosis in CD16 + and CD16 − subsets have been recently reported . The increased expression of glucocorticoid receptors on CD16 + may suggest subset‐specific mechanisms involved in the regulation of monocyte numbers.…”