title: Unique proteomic signatures distinguish macrophages and dendritic cells.
abstract: Monocytes differentiate into heterogeneous populations of tissue macrophages and dendritic cells (DCs) that regulate inflammation and immunity. Identifying specific populations of myeloid cells in vivo is problematic, however, because only a limited number of proteins have been used to assign cellular phenotype. Using mass spectrometry and bone marrow-derived cells, we provided a global view of the proteomes of M-CSF-derived macrophages, classically and alternatively activated macrophages, and GM-CSF-derived DCs. Remarkably, the expression levels of half the plasma membrane proteins differed significantly in the various populations of cells derived in vitro. Moreover, the membrane proteomes of macrophages and DCs were more distinct than those of classically and alternatively activated macrophages. Hierarchical cluster and dual statistical analyses demonstrated that each cell type exhibited a robust proteomic signature that was unique. To interrogate the phenotype of myeloid cells in vivo, we subjected elicited peritoneal macrophages harvested from wild-type and GM-CSF-deficient mice to mass spectrometric and functional analysis. Unexpectedly, we found that peritoneal macrophages exhibited many features of the DCs generated in vitro. These findings demonstrate that global analysis of the membrane proteome can help define immune cell phenotypes in vivo.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, United States of America. levb@uchicago.edu
authors.forename: Lev
authors.initials: L
authors.lastname: Becker
authors.forename: Ning-Chun
authors.initials: NC
authors.lastname: Liu
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Averill
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pamir
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Peng
authors.forename: Angela D
authors.initials: AD
authors.lastname: Irwin
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Fu
authors.forename: Karin E
authors.initials: KE
authors.lastname: Bornfeldt
authors.forename: Jay W
authors.initials: JW
authors.lastname: Heinecke
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism*; D002853:Chromatography, Liquid; D003713:Dendritic Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D053719:Tandem Mass Spectrometry
chemical_list: D020543:Proteome