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

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 (hMphi) and in atherosclerotic lesions. Contrary to the earlier report, hSR-BI mRNA was expressed in cultured hMphi and markedly upregulated with differentiation, determined by Northern blot and reverse transcriptase-based polymerase chain reaction analyses. The mRNA expression pattern during differentiation of hMphi 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 hMphi to understand the biological utility of this molecule.