slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation.

Abstract

Human monocytes are subdivided into classical, intermediate, and nonclassical subsets, but there is no unequivocal strategy to dissect the latter 2 cell types. We show herein that the cell surface marker 6-sulfo LacNAc (slan) can define slan-positive CD14(+)CD16(++) nonclassical monocytes and slan-negative CD14(++)CD16(+) intermediate monocytes. Gene expression profiling confirms that slan-negative intermediate monocytes show highest expression levels of major histocompatibility complex class II genes, whereas a differential ubiquitin signature is a novel feature of the slan approach. In unsupervised hierarchical clustering, the slan-positive nonclassical monocytes cluster with monocytes and are clearly distinct from CD1c(+) dendritic cells. In clinical studies, we show a selective increase of the slan-negative intermediate monocytes to >100 cells per microliter in patients with sarcoidosis and a fivefold depletion of the slan-positive monocytes in patients with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), which is caused by macrophage colony-stimulating factor (M-CSF) receptor mutations. These data demonstrate that the slan-based definition of CD16-positive monocyte subsets is informative in molecular studies and in clinical settings.

• Authors: Thomas P Hofer, Adam M Zawada, Marion Frankenberger, Kerstin Skokann, Anna A Satzl, Wolfgang Gesierich, Madeleine Schuberth, Johannes Levin, Adrian Danek, Björn Rotter, Gunnar H Heine, Loems Ziegler-Heitbrock
• Journal: Blood (Blood) Vol. 126 Issue 24 Pg. 2601-10 (Dec 10 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 26443621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society of Hematology.

Chemical References

• 6-sulfo-LacNac
• Amino Sugars
• Antigens, CD1
• CD1C protein, human
• FCGR3B protein, human
• GPI-Linked Proteins
• Glycoproteins
• HLA-D Antigens
• Lipopolysaccharide Receptors
• Receptors, IgG
• Receptor, Macrophage Colony-Stimulating Factor

Topics

• Amino Sugars (analysis)
• Antigens, CD1 (analysis)
• Dendritic Cells (chemistry)
• Female
• Flow Cytometry
• GPI-Linked Proteins (analysis)
• Gene Expression Profiling
• Genes, MHC Class II
• Genome-Wide Association Study
• Glycoproteins (analysis)
• HLA-D Antigens (analysis)
• Humans
• Immunomagnetic Separation
• Leukoencephalopathies (genetics, immunology, pathology)
• Lipopolysaccharide Receptors (analysis)
• Male
• Middle Aged
• Monocytes (chemistry, classification, immunology)
• Point Mutation
• Receptor, Macrophage Colony-Stimulating Factor (genetics)
• Receptors, IgG (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Sarcoidosis (immunology, pathology)
• Young Adult