Extracellular matrix metalloproteinase inducer (EMMPRIN) is induced upon monocyte differentiation and is expressed in human atheroma.
OBJECTIVE
Because extracellular matrix metalloproteinase inducer (EMMPRIN), a tumor cell-derived protein, induces matrix metalloproteinases (MMPs) in fibroblasts and because MMPs are important in atheroma formation, we investigated if EMMPRIN was expressed in granulocyte/macrophage-colony stimulating factor (GM-CSF)-differentiated human peripheral blood monocytes (HPBM) and macrophage foam cells. In addition, EMMPRIN was studied for its expression in human atheroma.


RESULTS
After 10 days of GM-CSF-induced monocyte differentiation, EMMPRIN mRNA increased 5- to 8-fold relative to undifferentiated monocytes. GM-CSF treatment of HPBM revealed that both EMMPRIN mRNA and protein were upregulated by day 2 over undifferentiated monocytes. GM-CSF-differentiated HPBM showed characteristic macrophage phenotype by showing increases in pancake-like morphology and increases in biochemical markers such as apolipoprotein E, MMP-9, and cholesterol ester (CE). While acetylated LDL treatment of the 10-day GM-CSF-differentiated HPBM increased CE mass 13- to 321-fold, EMMPRIN expression was unchanged relative to nonlipid-loaded macrophages. In human coronary atherosclerotic samples, EMMPRIN was observed in CD68(+) macrophage-rich areas as well as areas of MMP-9 expressions.


CONCLUSIONS
Based on these data, we conclude that monocyte differentiation induces EMMPRIN expression, CE enrichment of foam cells has no further effect on EMMPRIN expression, and EMMPRIN is present in human atheroma. Therefore, EMMPRIN may play a role in atherosclerosis development.
Major
Terry C
TC
Cardiovascular Pharmacology, Pfizer Global Research & Development, Pfizer, Inc, Ann Arbor, Mich 48105, USA. terry.major@pfizer.com
Liang
Liang
L
Lu
Xiaokang
X
Rosebury
Wendy
W
Bocan
Thomas M A
TM
D000328:Adult; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm; D001161:Arteriosclerosis / Q000503:physiopathology*; D051926:Basigin; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005110:Extracellular Space / Q000201:enzymology*; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D050356:Lipid Metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm; D051926:Basigin; D002784:Cholesterol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020781:Matrix Metalloproteinase 1; D020780:Matrix Metalloproteinase 9; D008562:Membrane Glycoproteins; C497886:BSG protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule