A National University of Ireland Galway REMEDI-Cúram-NEPHSTROM- funded study ‘Phenotypic and functional heterogeneity of human intermediate monocytes based on HLA-DR expression’ has been recently published in Immunology & Cell Biology. The body of research by Connaughton EP, Naicker S, Hanley SA, Slevin SM, Eykelenboom JK, Lowndes NF, O’Brien T, Ceredig R, Griffin MD, and Dennedy MC was published on 5 March 2018.
Human blood monocytes are sub-classified as classical, intermediate and non-classical. In this study, it was shown that conventionally-defined human intermediate monocytes (IM) can be divided into two distinct subpopulations with mid- and high-level surface expression of HLA-DR (referred to as DRmid and DRhi IM). These IM subpopulations were phenotypically and functionally characterized in healthy adult blood by flow cytometry, migration assays and lipoprotein uptake assays. Their absolute numbers and proportions were then compared in blood samples from obese and non-obese adults. DRmid and DRhi IM differentially expressed several proteins including CD62L, CD11a, CX3CR1 and CCR2. Overall, the DRmid IM surface profile more closely resembled that of classical monocytes while DRhi IM were more similar to non-classical. However, in contrast to classical monocytes, DRmid IM migrated weakly to CCL2, had reduced intracellular calcium flux following CCR2 ligation and favored adherence to TNF-α-activated endothelium over transmigration. In lipid uptake assays, DRmid IM demonstrated greater internalization of oxidized and acetylated low density lipoprotein than DRhi IM. In obese compared to non-obese adults, proportions and absolute numbers of DRmid , but not DRhi IM, were increased in blood. The results are consistent with phenotypic and functional heterogeneity within the IM subset that may be of specific relevance to lipoprotein scavenging and metabolic health.
doi: 10.1111/imcb.12032. [Epub ahead of print]