Expression of Human Scavenger Receptor Class B Type I in Cultured Human Monocyte-Derived Macrophages and Atherosclerotic Lesions

Abstract

Abstract-The scavenger receptor class B type I (SR-BI) and its human homologue CLA-1 (CD36 and LIMPII Analogous-1) have recently been identified to bind HDL and mediate the selective uptake of HDL lipids. Tissue distribution of both murine and human receptors is quite similar, in that they are expressed abundantly in liver and steroidogenic tissues. However, expression and function of the human SR-BI (hSR-BI), in the periphery of reverse cholesterol transport such as macrophages, are still unclear. In the present study, we have raised two different kinds of anti-hSR-BI polypeptide antibodies (Abs): one against the extracellular domain and the other against the intracellular domain. We have investigated the expression of hSR-BI mRNA and immunoreactive mass in freshly isolated cultured human monocyte-derived macrophages (hM) and in atherosclerotic lesions. Contrary to the earlier report, hSR-BI mRNA was expressed in cultured hM and markedly upregulated with differentiation, determined by Northern blot and reverse transcriptase-based polymerase chain reaction analyses. The mRNA expression pattern during differentiation of hM was very similar to those of SR class A and another member of SR class B, CD36. Protein expression was confirmed by Western blot analyses with the above Abs to show a major 83-kDa band. Modified lipoproteins such as oxidized LDL and acetylated LDL induced a 5-fold increase in mRNA and protein expression of hSR-BI. Confocal immunofluorescence microscopy demonstrated that hSR-BI immunoreactive mass was detectable as a heterogeneous, punctate staining pattern. Furthermore, immunohistochemical analysis showed that immunoreactive mass of hSR-BI was detected in foam cells in human aortic atherosclerotic lesions and that there was no significant difference of staining patterns between the two Abs. This study clearly demonstrates that hSR-BI is expressed in the lipid-laden macrophages in human atherosclerotic lesions, suggesting that it is very important to know its function and regulation in hM to understand the biological utility of this molecule. (Circ Res. 1999;85:108-116.)

Glycoxidised LDL isolated from subjects with impaired glucose tolerance increases CD36 and peroxisome proliferator–activator receptor γ gene expression in macrophages

“…Alternatively, its function in the uptake of modified lipoproteins might promote foam cell formation, rendering macrophage SCARB1 a proatherogenic factor. Previous in vitro studies have shown that oxLDL-induced changes in SCARB1 mRNA expression may be dependent on the differentiation status of the investigated cells, with transcription upregulated in the early differentiation stage [40,41] and downregulated in fully differentiated macrophages [11,40]. The lack of difference in the rates of SCARB1 expression stimulated by LDL from NGT and IGT subjects in the present study suggests that, in contrast to CD36, macrophage expression of SCARB1 is less sensitive to changes in LDL glycoxidation status.…”

Serum Amyloid A Is a Ligand for Scavenger Receptor Class B Type I and Inhibits High Density Lipoprotein Binding and Selective Lipid Uptake

“…SAA uptake into macrophages is strongly dependent on cell surface heparan sulfate binding to SAA (41) and occurs via a clathrin-dependent pathway (41). SR-BI is expressed in activated macrophages (42), but its contribution in these cells to HDL-selective lipid uptake, or SAA uptake, is unclear.…”

Class B Scavenger Receptors CD36 and SR-BI Are Receptors for Hypochlorite-modified Low Density Lipoprotein

“…In parallel, SR-BI contributes to cellular cholesterol efflux from peripheral tissues, the first step during reverse cholesterol transport. SR-BI is also present in monocyte/macrophages including THP-1 cells (30), where it could function as a true ox-LDL receptor by displaying many of the features characteristic for classical scavenger receptors including uptake and degradation of oxidized lipoproteins (66). Braun and co-workers (67) report that the loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disease, spontaneous myocardial infarctions, severe cardiac dysfunction, and premature death in apolipoprotein E-deficient mice.…”

“…29). Although SR-BI in comparison to SR-A and CD36 is less abundant in atherosclerotic lesions, its mRNA expression pattern during differentiation of human macrophages is similar to SR-AI and CD36, and both Cu-ox-LDL and ac-LDL may up-regulate its expression (30). Previous studies suggested that the primary routes for entry of ligands by macrophages are coated pits or caveolin-dependent endocytosis and/or phagocytosis.…”