Enzymatically degraded LDL preferentially binds to CD14(high) CD16(+) monocytes and induces foam cell formation mediated only in part by the class B scavenger-receptor CD36.
Heterogeneity of peripheral blood monocytes is characterized by specific patterns in the membrane expression of Fc gamma-receptor III (FcgammaRIII/CD16) and the lipopolysaccharide receptor (LPS receptor CD14), allowing discrimination of distinct subpopulations. The aim was to analyze the correlation of these phenotypic differences to the early interaction of freshly isolated monocytes with modified lipoproteins by the use of either enzymatically degraded low density lipoprotein (E-LDL), acetylated low density lipoprotein (ac-LDL), oxidized low density lipoprotein (ox-LDL), or native low density lipoprotein. Highest E-LDL binding was observed on CD14(high) CD16(+) monocytes as determined by flow cytometry, suggesting a selective interaction of E-LDL with distinct subpopulations of monocytes. E-LDL induced rapid foam cell formation both in predifferentiated monocyte-derived macrophages and, in contrast to ac-LDL or ox-LDL, also in freshly isolated peripheral blood monocytes. This was accompanied by upregulation of the 2 class B scavenger receptors CLA-1/SR-BI (CD36 and LIMPII Analogous-1/scavenger receptor type B class I) and CD36. Cellular binding and uptake of E-LDL was neither competed by ac-LDL nor the class A scavenger-receptor inhibitor polyinosinic acid but was partially inhibited by an excess of ox-LDL. In predifferentiated monocyte-derived macrophages, an anti-CD36 antibody inhibited cellular binding and uptake of E-LDL by approximately 20%, suggesting that recognition of these hydrolase-modified low density lipoprotein particles is mediated only in part by the class B scavenger receptor CD36.
Kapinsky
M
M
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
Torzewski
M
M
Büchler
C
C
Duong
C Q
CQ
Rothe
G
G
Schmitz
G
G
D000345:Affinity Labels / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002232:Carbocyanines / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008565:Membrane Proteins; D009000:Monocytes / Q000378:metabolism*; D011069:Poly I / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017452:Receptors, IgG / Q000032:analysis*; D011971:Receptors, Immunologic; D011973:Receptors, LDL / Q000502:physiology; D018110:Receptors, Lipoprotein / Q000096:biosynthesis / Q000235:genetics; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D015854:Up-Regulation
D000345:Affinity Labels; D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D002232:Carbocyanines; D008055:Lipids; D018950:Lipopolysaccharide Receptors; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D012333:RNA, Messenger; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; D011069:Poly I; C024286:3,3'-dioctadecylindocarbocyanine