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

Monocytes, key components of the immune system, are a heterogeneous population comprised of classical monocytes (CD16(-)) and non-classical monocytes (CD16(+)). Monocytes are short lived and undergo spontaneous apoptosis, unless stimulated. Dysregulation of monocyte numbers contribute to the pathophysiology of inflammatory diseases, yet the contribution of each subset remains poorly characterized. Protein kinase C (PKC) family members are central to monocyte biology; however, their role in regulating lifespan and immune function of CD16(-) and CD16(+) monocytes has not been studied. Here, we evaluated the contribution of PKC and PKC epsilon in the lifespan and immune response of both monocyte subsets. We showed that CD16(+) monocytes are more susceptible to spontaneous apoptosis because of the increased caspase-3, -8 and -9 activities accompanied by higher kinase activity of PKC. Silencing of PKC reduced apoptosis in both CD16(+) and CD16(-) monocytes. CD16(+) monocytes express significantly higher levels of PKC epsilon and produce more tumour necrosis factor- in CD16(+) compared with CD16(-) monocytes. Silencing of PKC epsilon affected the survival and tumour necrosis factor- production. These findings demonstrate a complex network with similar topography, yet unique regulatory characteristics controlling lifespan and immune response in each monocyte subset, helping define subset-specific coordination programmes controlling monocyte function.