Differential expression of the EGF-TM7 family members CD97 and EMR2 in lipid-laden macrophages in atherosclerosis, multiple sclerosis and Gaucher disease.
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.
van Eijk
Marco
M
Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. m.c.vaneijk@amc.uva.nl
Aust
Gabriela
G
Brouwer
Michael S M
MS
van Meurs
Marjan
M
Voerman
Jane S A
JS
Dijke
I Esmé
IE
Pouwels
Walter
W
Sändig
Irene
I
Wandel
Elke
E
Aerts
Johannes M F G
JM
Boot
Rolf G
RG
Laman
Jon D
JD
Hamann
Jörg
J
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
C412456:ADGRE2 protein, human; C095004:ADGRE5 protein, human; D015703:Antigens, CD; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled