title: 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.affiliation: The EvA Study Center, Comprehensive Pneumology Center, Helmholtz-Zentrum München, Gauting, Germany;
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Hofer
authors.affiliation: Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany;
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zawada
authors.affiliation: The EvA Study Center, Comprehensive Pneumology Center, Helmholtz-Zentrum München, Gauting, Germany;
authors.forename: Marion
authors.initials: M
authors.lastname: Frankenberger
authors.affiliation: The EvA Study Center, Comprehensive Pneumology Center, Helmholtz-Zentrum München, Gauting, Germany;
authors.forename: Kerstin
authors.initials: K
authors.lastname: Skokann
authors.affiliation: Asklepios Fachklinik München-Gauting, German Center for Lung Research, Gauting, Germany;
authors.forename: Anna A
authors.initials: AA
authors.lastname: Satzl
authors.affiliation: Asklepios Fachklinik München-Gauting, German Center for Lung Research, Gauting, Germany;
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gesierich
authors.affiliation: Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, München, Germany; and.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Schuberth
authors.affiliation: Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, München, Germany; and.
authors.forename: Johannes
authors.initials: J
authors.lastname: Levin
authors.affiliation: Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, München, Germany; and.
authors.forename: Adrian
authors.initials: A
authors.lastname: Danek
authors.affiliation: GenXPro, Frankfurt, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Rotter
authors.affiliation: Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany;
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
authors.affiliation: The EvA Study Center, Comprehensive Pneumology Center, Helmholtz-Zentrum München, Gauting, Germany;
authors.forename: Loems
authors.initials: L
authors.lastname: Ziegler-Heitbrock
mesh_terms: D000606:Amino Sugars / Q000032:analysis*; D018949:Antigens, CD1 / Q000032:analysis; D003713:Dendritic Cells / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000032:analysis; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II; D055106:Genome-Wide Association Study; D006023:Glycoproteins / Q000032:analysis; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D018189:Immunomagnetic Separation; D056784:Leukoencephalopathies / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000145:classification* / Q000276:immunology; D017354:Point Mutation; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics*; D017452:Receptors, IgG / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012507:Sarcoidosis / Q000276:immunology / Q000473:pathology; D055815:Young Adult
chemical_list: C467438:6-sulfo-LacNac; D000606:Amino Sugars; D018949:Antigens, CD1; C437944:CD1C protein, human; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D006681:HLA-D Antigens; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D016186:Receptor, Macrophage Colony-Stimulating Factor