Acetylated LDL endocytosis by the human monocytic Mono Mac 6sr cells is not mediated by the macrophage type I and II scavenger receptors.
We recently reported that the human monocytic Mono Mac 6sr cell line constitutively takes up and degrades acetylated (acLDL) and oxidized LDL through receptor-specific pathways. The present studies were undertaken to further characterize the acLDL binding site on a functional and molecular basis. The degradation of acLDL increased during differentiation of Mono Mac 6sr cells with lipopolysaccharide (10 ng/mL, 72 hours) and low concentrations of phorbol 12-myristate 13-acetate (PMA; 0.1 to 1.0 ng/mL, 72 hours). Higher doses of PMA (5 or 10 ng/mL), however, decreased acLDL degradation. Scatchard plots of acLDL binding in untreated and LPS-differentiated Mono Mac 6sr cells were nonlinear and suggested the presence of more than one binding site. Although the ligand specificity of the acLDL receptor in Mono Mac 6sr cells resembles that of the macrophage type I and type II scavenger receptors, we did not detect mRNA of either receptor type in untreated or differentiated Mono Mac 6sr cells by means of Northern blotting and reverse transcription polymerase chain reaction. Furthermore, ligand blotting with 125I-acLDL failed to detect the 220-kD types I and II scavenger receptor protein. Thus, Mono Mac 6sr cells express an acLDL receptor that is distinct from the type I and type II scavenger receptor found in human monocyte-derived macrophages but that, like the latter, is induced during monocytic differentiation.
Scheithe
R
R
Institut für Prophylaxe und Epidemiologie, Kreislaufkrankheiten, Ludwig-Maximilians-Universität, Munich, Germany.
Heidenthal
A K
AK
Danesch
U
U
Mauthner
E
E
Hapfelmeier
G
G
Becker
A
A
Pietsch
A
A
Weber
P C
PC
Hrboticky
N
N
D002454:Cell Differentiation; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004705:Endocytosis; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008565:Membrane Proteins; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D008024:Ligands; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C032629:acetyl-LDL; D002784:Cholesterol