title: Differential expression of the EGF-TM7 family members CD97 and EMR2 in lipid-laden macrophages in atherosclerosis, multiple sclerosis and Gaucher disease.
abstract: The members of the epidermal growth factor (EGF)-transmembrane (TM)7 family of adhesion class G-protein coupled receptors are abundantly expressed by cells of the myeloid lineage. A detailed investigation of their expression by functional subsets of activated macrophages is still lacking. Therefore, we determined the expression of CD97, EGF module-containing mucin-like receptor (EMR)2 and EMR3 by monocyte-derived macrophages experimentally polarized in vitro. This was compared to three types of disease-associated lipid-laden macrophages displaying an alternatively activated phenotype in situ. Polarization in vitro towards classically activated M1 versus alternatively activated M2 extremes of macrophage activation did not result in a congruent regulation of EGF-TM7 receptor mRNA and protein except for a down-regulation of CD97 by IL-10. In contrast, macrophages handling lipid overload in vivo displayed differences in the expression of CD97 and EMR2. While foamy macrophages in atherosclerotic vessels expressed both CD97 and EMR2, foam cells in multiple sclerosis brain expressed CD97, but only little EMR2. Foam cell formation in vitro by oxidized LDL and myelin did not affect CD97 or EMR2 expression. Gaucher spleen cells accumulating glucosylceramide expressed very high levels of CD97 and EMR2. These findings indicate that complex cellular expression programmes rather than activation modes regulate the expression of EGF-TM7 receptors in macrophages.
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. m.c.vaneijk@amc.uva.nl
authors.forename: Marco
authors.initials: M
authors.lastname: van Eijk
authors.forename: Gabriela
authors.initials: G
authors.lastname: Aust
authors.forename: Michael S M
authors.initials: MS
authors.lastname: Brouwer
authors.forename: Marjan
authors.initials: M
authors.lastname: van Meurs
authors.forename: Jane S A
authors.initials: JS
authors.lastname: Voerman
authors.forename: I Esmé
authors.initials: IE
authors.lastname: Dijke
authors.forename: Walter
authors.initials: W
authors.lastname: Pouwels
authors.forename: Irene
authors.initials: I
authors.lastname: Sändig
authors.forename: Elke
authors.initials: E
authors.lastname: Wandel
authors.forename: Johannes M F G
authors.initials: JM
authors.lastname: Aerts
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Boot
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology*; D002339:Carotid Arteries / Q000276:immunology; D005434:Flow Cytometry; D005776:Gaucher Disease / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C412456:ADGRE2 protein, human; C095004:ADGRE5 protein, human; D015703:Antigens, CD; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled