title: Novel Markers to Delineate Murine M1 and M2 Macrophages.
abstract: Classically (M1) and alternatively activated (M2) macrophages exhibit distinct phenotypes and functions. It has been difficult to dissect macrophage phenotypes in vivo, where a spectrum of macrophage phenotypes exists, and also in vitro, where low or non-selective M2 marker protein expression is observed. To provide a foundation for the complexity of in vivo macrophage phenotypes, we performed a comprehensive analysis of the transcriptional signature of murine M0, M1 and M2 macrophages and identified genes common or exclusive to either subset. We validated by real-time PCR an M1-exclusive pattern of expression for CD38, G-protein coupled receptor 18 (Gpr18) and Formyl peptide receptor 2 (Fpr2) whereas Early growth response protein 2 (Egr2) and c-Myc were M2-exclusive. We further confirmed these data by flow cytometry and show that M1 and M2 macrophages can be distinguished by their relative expression of CD38 and Egr2. Egr2 labeled more M2 macrophages (~70%) than the canonical M2 macrophage marker Arginase-1, which labels 24% of M2 macrophages. Conversely, CD38 labeled most (71%) in vitro M1 macrophages. In vivo, a similar CD38+ population greatly increased after LPS exposure. Overall, this work defines exclusive and common M1 and M2 signatures and provides novel and improved tools to distinguish M1 and M2 murine macrophages.
authors.affiliation: School of Health and Rehabilitation Sciences, Medical Laboratory Science Division, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Jablonski
authors.affiliation: School of Health and Rehabilitation Sciences, Medical Laboratory Science Division, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Amici
authors.affiliation: School of Health and Rehabilitation Sciences, Medical Laboratory Science Division, The Ohio State University, Columbus, Ohio, United States of America.|Biomedical Sciences Graduate Program, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Webb
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Juan de Dios
authors.initials: Jde D
authors.lastname: Ruiz-Rosado
authors.affiliation: Department of Neuroscience, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Popovich
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Santiago
authors.initials: S
authors.lastname: Partida-Sanchez
authors.affiliation: School of Health and Rehabilitation Sciences, Medical Laboratory Science Division, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Mireia
authors.initials: M
authors.lastname: Guerau-de-Arellano
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D005434:Flow Cytometry; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D008070:Lipopolysaccharides; D012333:RNA, Messenger