Hepatic SR-BI-mediated cholesteryl ester selective uptake occurs with unaltered efficiency in the absence of cellular energy

Scavenger receptor class B type I (SR-BI) plays a critical role in the delivery of HDL cholesterol and cholesteryl esters (CEs) to liver and steroidogenic tissues by a selective process that does not result in significant degradation of HDL protein. Recently, SR-BI-mediated endocytosis and recycling of HDL have been demonstrated. However, it remains unclear whether efficient SR-BI-mediated selective uptake occurs strictly at the plasma membrane or at additional sites along its endocytic itinerary. To examine the requirement for SR-BI endocytosis in HDL selective uptake, we determined the effects of energy depletion on the levels of cell-associated HDL protein and CE in primary mouse hepatocytes. Compared with CHO cells, we observed a much larger energy-dependent effect on CE uptake in primary mouse hepatocytes. Although varying the levels of caveolin-1 and carboxyl ester lipase altered the efficiency of selective uptake, neither was able to account for the energy-dependent component of HDL-CE uptake. Finally, we demonstrate that the hepatocyte-specific, energy-dependent effects on HDL-apolipoprotein A-I and -CE uptake are independent of SR-BI and are not required to achieve efficient SR-BI-mediated selective uptake of CE. Together, these data support the conclusion that neither the intracellular trafficking of HDL nor any energy-dependent cellular process affects the ability of the cell to maximally acquire CE through SR-BI-mediated selective uptake from HDL. Scavenger receptor class B type I (SR-BI) plays a critical role in the delivery of HDL cholesterol and cholesteryl esters (CEs) to liver and steroidogenic tissues by a selective process that does not result in significant degradation of HDL protein. Recently, SR-BI-mediated endocytosis and recycling of HDL have been demonstrated. However, it remains unclear whether efficient SR-BI-mediated selective uptake occurs strictly at the plasma membrane or at additional sites along its endocytic itinerary. To examine the requirement for SR-BI endocytosis in HDL selective uptake, we determined the effects of energy depletion on the levels of cell-associated HDL protein and CE in primary mouse hepatocytes. Compared with CHO cells, we observed a much larger energy-dependent effect on CE uptake in primary mouse hepatocytes. Although varying the levels of caveolin-1 and carboxyl ester lipase altered the efficiency of selective uptake, neither was able to account for the energy-dependent component of HDL-CE uptake. Finally, we demonstrate that the hepatocyte-specific, energy-dependent effects on HDL-apolipoprotein A-I and -CE uptake are independent of SR-BI and are not required to achieve efficient SR-BI-mediated selective uptake of CE. Together, these data support the conclusion that neither the intracellular trafficking of HDL nor any energy-dependent cellular process affects the ability of the cell to maximally acquire CE through SR-BI-mediated selective uptake from HDL. HDL has a functional role in the protection against atherosclerosis, and its plasma concentration is inversely correlated with the risk of cardiovascular disease. One of the protective actions of HDL involves cholesterol removal from peripheral cells for transport to the liver for biliary secretion (reviewed in 1Connelly M.A. Williams D.L. Scavenger receptor BI: a scavenger receptor with a mission to transport high density lipoprotein lipids.Curr. Opin. Lipidol. 2004; 15: 287-295Google Scholar). This process, termed “reverse cholesterol transport,” is mediated, in part, by the well-established HDL receptor, scavenger receptor class B type I (SR-BI) (2Acton S. Rigotti A. Landschulz K.T. Xu S. Hobbs H.H. Krieger M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor.Science. 1996; 271: 518-520Google Scholar). In contrast to the holoparticle uptake of the LDL pathway (3Brown M.S. Goldstein J.L. A receptor-mediated pathway for cholesterol homeostasis.Science. 1986; 232: 34-47Google Scholar), SR-BI mediates cholesterol, cholesteryl ester (CE), and phospholipid uptake via a pathway that does not involve significant degradation of the HDL particle, a process known as “selective uptake.” This process was originally described to consist of two phases. First, the lipoprotein binds to SR-BI on the cell surface, and second, the lipids in the lipoprotein are transferred to a membrane (reviewed in 1Connelly M.A. Williams D.L. Scavenger receptor BI: a scavenger receptor with a mission to transport high density lipoprotein lipids.Curr. Opin. Lipidol. 2004; 15: 287-295Google Scholar). Despite intense interest in SR-BI, the cellular mechanism by which SR-BI contributes to the selective uptake and intracellular trafficking of HDL-derived CE is still not fully understood. Early kinetic studies demonstrated that the rate of CE transfer is proportional to the amount of CE in HDL, suggesting that SR-BI forms a hydrophobic channel that facilitates the movement of sterol down a concentration gradient into the plasma membrane (4Rodrigueza W.V. Thuahnai S.T. Temel R.E. Lund-Katz S. Phillips M.C. Williams D.L. Mechanism of scavenger receptor class B type I-mediated selective uptake of cholesteryl esters from high density lipoprotein to adrenal cells.J. Biol. Chem. 1999; 274: 20344-20350Google Scholar). Experiments involving reconstitution of SR-BI into liposomes showed that SR-BI mediates CE selective uptake from HDL into multilamellar vesicles independent of cellular cofactors (5Liu B. Krieger M. Highly purified scavenger receptor class B, type I reconstituted into phosphatidylcholine/cholesterol liposomes mediates high affinity high density lipoprotein binding and selective lipid uptake.J. Biol. Chem. 2002; 277: 34125-34135Google Scholar). These data are consistent with a model in which HDL binding to SR-BI is sufficient to mediate the diffusional transfer of CE into the plasma membrane. However, these studies did not address the potential role of other cellular processes in accelerating CE transfer. Accordingly, defects in HDL internalization have been suggested to decrease the selective uptake of CE (6Silver D.L. Wang N. Tall A.R. Defective HDL particle uptake in ob/ob hepatocytes causes decreased recycling, degradation, and selective lipid uptake.J. Clin. Invest. 2000; 105: 151-159Google Scholar). HDL recycling, analogous to the internalization and recycling of transferrin and its receptor, was speculated to play a role in efficient selective uptake (7Silver D.L. Wang N. Xiao X. Tall A.R. High density lipoprotein (HDL) particle uptake mediated by scavenger receptor class B type 1 results in selective sorting of HDL cholesterol from protein and polarized cholesterol secretion.J. Biol. Chem. 2001; 276: 25287-25293Google Scholar). Subsequent studies indicated that SR-BI mediated HDL endocytosis and recycling, with concurrent depletion of HDL lipids (8Rhainds D. Bourgeois P. Bourret G. Huard K. Falstrault L. Brissette L. Localization and regulation of SR-BI in membrane rafts of HepG2 cells.J. Cell Sci. 2004; 117: 3095-3105Google Scholar). However, other data supported the conclusion that efficient selective uptake of CE does not require endocytosis (9Pittman R.C. Knecht T.P. Rosenbaum M.S. Taylor Jr., C.A. A nonendocytotic mechanism for the selective uptake of high density lipoprotein-associated cholesterol esters.J. Biol. Chem. 1987; 262: 2443-2450Google Scholar, 10Eckhardt E.R. Cai L. Sun B. Webb N.R. van der Westhuyzen D.R. High density lipoprotein uptake by scavenger receptor SR-BII.J. Biol. Chem. 2004; 279: 14372-14381Google Scholar, 11Nieland T.J. Ehrlich M. Krieger M. Kirchhausen T. Endocytosis is not required for the selective lipid uptake mediated by murine SR-BI.Biochim. Biophys. Acta. 2005; 1734: 44-51Google Scholar). To address these discrepancies, we examined the requirement for endocytosis for selective uptake of CE in both steroidogenic cells and hepatocytes. We confirm that in CHO cells, a block in endocytosis has no effect on the efficiency of CE selective uptake. Furthermore, we determine that in primary mouse hepatocytes, efficient CE selective uptake also occurs despite blocking HDL endocytosis and demonstrate that in hepatocytes, SR-BI mediates a very small fraction of total HDL endocytosis. Cycloheximide, 2-deoxyglucose, monensin, NaN3, and HBSS were from was from and were from and protein and cholesteryl were from was from and was from SR-BI protein and protein were by of the and into the and were consistent with as determined by was by of protein was from by the and has been L. A. endocytosis of a pathway to the Cell Biol. 2001; Scholar). CHO cells were in with and were and to the of of and of of a cells were in cells of and with cells were by M. of the mouse were from and were from the were from with were with to and and were on a on a hepatocytes were from these to L. of and cells on in of Scholar, E.R. M. of on liver cell and Biophys. Acta. Scholar). were and were with cells were on at density of cells in and the the cells were in and was cells were the HDL was purified by density gradient plasma from a D. of and of by Scholar). HDL of of cholesterol, of and of of HDL protein. were against of with of for a of purified HDL was with or G. P. density lipoprotein protein contributes to selective uptake of high density lipoprotein cholesteryl esters by cells and primary Biol. Chem. 2001; 276: Scholar). A total of of A-I by D. L. of was in two in with of of G. P. density lipoprotein protein contributes to selective uptake of high density lipoprotein cholesteryl esters by cells and primary Biol. Chem. 2001; 276: Scholar). was HDL by a density and of the HDL was as described of the of HDL and was purified by on a and was with of a of as described for HDL was also a protein One to of protein was the and from on a was at to protein of HDL was with at of two to the was at the was the cell with HDL. HDL was as described L. S. in the transport of cholesteryl esters.J. Biol. Chem. 1996; 271: Scholar). of HDL was sufficient of the was in the of the HDL particle in a as in of cells cells or primary mouse hepatocytes were on at with of and and in for with or with and were at with the for the the of the the was and cells were on with In the of at with the the the was and the cells were with of at with protein of from was a and the protein to the cell-associated or in of cell was by or by cell or degradation of was in of the amount of in 1 of HDL and for levels of total cell is required for and in HDL endocytosis in cells, does not at or with energy Cell described in and cells were with protein with for at with and in a cell with HDL and SR-BI endocytic were at the of the observed a is cells with were with energy depletion as described for with of were with and a of SR-BI affects the efficiency of selective uptake from HDL does in mouse hepatocytes from and were with or depletion for at the of the primary mouse hepatocytes from were and with of of or or of SR-BI for or was to the were for and as described of carboxyl ester lipase with the efficiency of selective uptake in mouse hepatocytes from were and for to the levels of from these cells was and were with or depletion for at the of the A total of of the was with or were for and as described of affects the efficiency of selective uptake from HDL does in mouse hepatocytes from and were with or depletion for at the of the primary mouse hepatocytes from were and with of of or of for A total of of or was to the were for and as described is required for energy-dependent CE uptake in primary mouse hepatocytes. were with or for at the of the and and and and were and as described in and selective uptake is for both CE and in and energy depletion and energy is required for the efficient uptake of CE in primary mouse hepatocytes. were with or for at the of the and and and and were and as described in and selective uptake is for both CE and in and energy depletion and of the of and HDL, cells were on and with were in cell in with and with in 1 by for with to of the with a at and at with of and through a or were as the demonstrate cells that are of and that have been by at two independent and cells on were with on for to that the of the cells was were on with the was the cells were transferred to a and was a the cells were on with with and with were and as described for the selective uptake cells were with energy depletion and at for to of endocytosis. were in energy depletion with for with and examined for of were with a were a of and the or the of a was with a To address the requirement of HDL endocytosis for selective uptake, we endocytic processes by depletion of cellular energy with and D. M. A. transport for high density lipoprotein and its sterol in polarized cells.J. 2004; in two cell CHO cells the LDL receptor and primary mouse hepatocytes This of the of HDL the cell of and the levels of selective uptake in the of endocytosis. We both cells and primary mouse hepatocytes with as a to that endocytosis was with energy depletion from studies T.J. Ehrlich M. Krieger M. Kirchhausen T. Endocytosis is not required for the selective lipid uptake mediated by murine SR-BI.Biochim. Biophys. Acta. 2005; 1734: 44-51Google Scholar, M.A. Lund-Katz S. Phillips M.C. Williams D.L. Scavenger receptor (SR-BI) on that plasma membrane is a for cholesterol trafficking cells and Biol. 2004; 15: Scholar, M. S. that high density are not by cells in Clin. Invest. Scholar), binding to the cell was not in that HDL remains to the cell in CHO cells consistent with T.J. Ehrlich M. Krieger M. Kirchhausen T. Endocytosis is not required for the selective lipid uptake mediated by murine SR-BI.Biochim. Biophys. Acta. 2005; 1734: 44-51Google Scholar), we demonstrate that blocking endocytosis does not the cell of CE To that the rate of cell of CE is not by the of cholesterol from CE we also examined the uptake of the CE We energy depletion no effect on cell that CE account for these results D. M. A. transport for high density lipoprotein and its sterol in polarized cells.J. 2004; Scholar). at the in these uptake of CE occurs in a of HDL that CE cell is selective uptake energy depletion effect on the of cell in cells we determined whether HDL internalization occurs in these cells and whether endocytosis is on to cell HDL to data not we demonstrate that the of SR-BI at is required for internalization of HDL Although the of total HDL that internalization these data that HDL is a significant endocytic To SR-BI-mediated HDL we SR-BI with at the indicated that the is (2Acton S. Rigotti A. Landschulz K.T. Xu S. Hobbs H.H. Krieger M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor.Science. 1996; 271: 518-520Google Scholar), as indicated by a of the protein in to the at not We also observed suggesting the of S. A. S. of the scavenger receptor class B type and in cells and 2004; Scholar). In no degradation of the SR-BI were the of the HDL binding to the cell in and we observed of vesicles into the cell consistent with the endocytic uptake of HDL (7Silver D.L. Wang N. Xiao X. Tall A.R. High density lipoprotein (HDL) particle uptake mediated by scavenger receptor class B type 1 results in selective sorting of HDL cholesterol from protein and polarized cholesterol secretion.J. Biol. Chem. 2001; 276: 25287-25293Google Scholar). that HDL endocytosis is not required for selective uptake in cells, we examined the of CE in these cells a CE L. S. uptake by the pathway of intracellular Scholar). We that despite the of cellular levels of still in and with we that these are lipid the also in cell that along in a of cell These did not with that the been from by selective uptake. To we levels of in cells the cells of cellular and with from HDL by selective uptake. Although we did not of with not we did of and In contrast to cells, primary mouse hepatocytes much levels of HDL cell and selective uptake 1 two HDL cell CE cell and selective In energy depletion decreased the levels of cell-associated at that much of HDL holoparticle uptake in cell model with decreased HDL we also observed significant in CE and cell with energy depletion in these cells were no significant the levels of CE and cell that of CE is not a in the levels of cell energy that the in CE and cell with energy depletion to a block in HDL endocytosis or to any of cellular cofactors that require we endocytosis with We that and energy depletion effects on CE and cell and selective uptake, that a block in endocytosis total cellular of CE and in hepatocytes not in cells observed cell with energy depletion result from in the regulation of cofactors that the efficiency of selective uptake. is protein that has been to the efficiency of selective uptake S. van der Westhuyzen D.R. of scavenger and caveolin-1 is with selective cholesteryl ester uptake in 1999; Scholar). is able to transport CE in its levels in hepatocytes result in of CE concentration from HDL to the plasma membrane A. W.V. ester is from to as of a Biol. Chem. 2002; 277: Scholar, cholesterol account for the levels of CE uptake. we primary hepatocytes from and and examined the effect of on the selective uptake efficiency of the of CE at Although the of no of the efficiency of selective uptake with These confirm that is not required for selective uptake, that of have effect on the efficiency of selective uptake. However, despite any in uptake in the or of the of the with energy depletion the no effect on the energy-dependent cell of affects the efficiency of selective uptake in not involving endocytosis. cellular that has been to the efficiency of CE selective uptake is carboxyl ester lipase cholesterol uptake of high density lipoprotein-associated cholesteryl esters by HepG2 1996; Scholar). or lipase is in is also in hepatocytes ester and role in lipoprotein and 2002; Scholar). the efficiency of the SR-BI-mediated selective uptake of CE or by CE and a high CE concentration gradient ester lipase with scavenger receptor in lipid rafts and selective uptake and of cholesteryl esters from Biol. Chem. 2004; 279: Scholar). To examine the effect of on HDL cell we hepatocytes and the to in for were with or and to the cells for with or of cholesterol uptake of high density lipoprotein-associated cholesteryl esters by HepG2 1996; of with the efficiency of selective uptake from HDL with and was also independent of cellular that the energy-dependent decrease in cell was not mediated by and to require we that it was independent of To we primary hepatocytes from and and examined the effect of SR-BI on cell We that of SR-BI decreased the amount of cell-associated of SR-BI by in significant in cell We determined from these that the levels of SR-BI affects the selective uptake of by with SR-BI and by for of and by for of with has no effect on the energy-dependent endocytosis of HDL These studies demonstrate that neither endocytosis nor recycling of HDL is required for efficient SR-BI-mediated CE selective uptake in hepatocytes. We determined that CE from HDL selective uptake to in CHO cells and that the efficiency of CE selective uptake in hepatocytes. These the of CE trafficking in SR-BI-mediated selective uptake and that the of HDL endocytosis in hepatocytes is holoparticle uptake. that suggesting that HDL recycling a functional role in CE selective uptake were in cell (6Silver D.L. Wang N. Tall A.R. Defective HDL particle uptake in ob/ob hepatocytes causes decreased recycling, degradation, and selective lipid uptake.J. Clin. Invest. 2000; 105: 151-159Google Scholar, D. Bourgeois P. Bourret G. Huard K. Falstrault L. Brissette L. Localization and regulation of SR-BI in membrane rafts of HepG2 cells.J. Cell Sci. 2004; 117: 3095-3105Google Scholar), we originally that process cell Accordingly, we in primary hepatocytes to determine whether blocking endocytosis the efficiency of selective uptake. We to the of cholesterol to CE and to energy-dependent cellular endocytosis. However, the significant in HDL was a decrease in both and cell in hepatocytes in to energy depletion not in CHO cells and monensin, we that energy-dependent decrease was to a decrease in HDL endocytosis in hepatocytes that endocytosis was by or SR-BI These results that HDL endocytosis in primary mouse hepatocytes occurs of SR-BI and does not the efficiency of selective uptake. These results not the that CE selective uptake also occurs small of HDL are endocytosis for degradation, or However, that the of HDL endocytosis in hepatocytes is the of SR-BI-mediated CE selective uptake recycling these results not a role for in HDL recycling, nor that the intracellular trafficking or the of SR-BI in that SR-BI trafficking does not to the efficiency of SR-BI-mediated CE selective uptake. In that the cell of SR-BI the efficiency of selective uptake. the liver a binding protein that with the on the of SR-BI and its cell (reviewed in D.L. SR-BI and in high density lipoprotein 2004; Scholar, A. Rigotti A. Krieger M. of SR-BI-mediated lipoprotein by the protein Opin. Lipidol. 2005; Scholar). binding to SR-BI cell of intracellular SR-BI, mechanism for the intracellular trafficking of SR-BI in hepatocytes. However, the regulation of SR-BI by is very its in hepatocytes is to have results the of is also to that results the energy of selective uptake as the recycling of HDL and of However, has been for cholesterol and not and that were with the and of cholesterol of CE by is of the CE concentration gradient required for selective uptake in hepatocytes and is supported by of SR-BI and in cells ester lipase with scavenger receptor in lipid rafts and selective uptake and of cholesteryl esters from Biol. Chem. 2004; 279: Scholar). We as with the efficiency of selective uptake, was independent of cellular data are consistent with that the CE concentration gradient and SR-BI-mediated transfer ester lipase with scavenger receptor in lipid rafts and selective uptake and of cholesteryl esters from Biol. Chem. 2004; 279: Scholar). Although has been to with SR-BI ester lipase with scavenger receptor in lipid rafts and selective uptake and of cholesteryl esters from Biol. Chem. 2004; 279: Scholar), results that is not in CE selective uptake and that in the of HDL or also from these studies on the of to selective uptake. SR-BI has been to as a hydrophobic channel CE to transferred down a concentration gradient into the plasma membrane (4Rodrigueza W.V. Thuahnai S.T. Temel R.E. Lund-Katz S. Phillips M.C. Williams D.L. Mechanism of scavenger receptor class B type I-mediated selective uptake of cholesteryl esters from high density lipoprotein to adrenal cells.J. Biol. Chem. 1999; 274: 20344-20350Google Scholar). the CE concentration in the membrane the efficiency of CE transfer. of CE from the plasma membrane involve a endocytosis of in CE. in energy depletion and the endocytosis of in it is that the transfer of CE to the CE concentration gradient required for efficient selective uptake. we that despite the depletion of energy in cells, was able to to lipid of and it is that has and from the plasma membrane and these lipid However, is to the plasma membrane and the lipid it also to cells that the the that the has not altered the of CE. that is to lipid that is transport of CE in these Accordingly, of and CE have been to the intracellular of CE in CHO cells A. W.V. ester is from to as of a Biol. Chem. 2002; 277: Scholar). In of of was to the transport of CE to lipid A. W.V. ester is from to as of a Biol. Chem. 2002; 277: Scholar). We also observed a for the internalization of CE. both HDL protein and CE or were in was that CE selective uptake was that it and for HDL particle to of CE and from This transfer of CE was in of studies that both SR-BI and CE from HDL selective uptake to suggested that SR-BI and CE from HDL selective were to B. Rigotti A. Xu S. Krieger M. SR-BI, a high density lipoprotein receptor that mediates selective lipid uptake, is and and with plasma membrane Biol. Chem. Scholar, van der Westhuyzen D.R. class B, type I scavenger receptor the selective uptake of high density lipoprotein cholesterol into Biol. Chem. 1999; 274: Scholar). However, SR-BI was to in a membrane that was independent of (8Rhainds D. Bourgeois P. Bourret G. Huard K. Falstrault L. Brissette L. Localization and regulation of SR-BI in membrane rafts of HepG2 cells.J. Cell Sci. 2004; 117: 3095-3105Google Scholar, Rigotti A. A. depletion of the scavenger receptor class B type I in Sci. 2004; and to a that was independent of M.A. Lund-Katz S. Phillips M.C. Williams D.L. Scavenger receptor (SR-BI) on that plasma membrane is a for cholesterol trafficking cells and Biol. 2004; 15: Scholar, D. Brissette L. L. M. and of SR-BI in the Cell Sci. 2004; 117: Scholar). of the of SR-BI to (reviewed in 1Connelly M.A. Williams D.L. Scavenger receptor BI: a scavenger receptor with a mission to transport high density lipoprotein lipids.Curr. Opin. Lipidol. 2004; 15: 287-295Google Scholar), studies have the and CE we have that cell-associated in on the cell surface, play role in the internalization of CE in CHO Although the effects of are data support a model in which A. W.V. ester is from to as of a Biol. Chem. 2002; 277: the internalization of CE. we are not suggesting that or rafts are required for selective uptake S. A. G. SR-BI does not require for cholesteryl ester selective uptake in the adrenal cell Biophys. Acta. Scholar), as hepatocytes did not have decreased selective uptake. We the that plasma membrane CE for efficient selective uptake and that in hepatocytes, also that selective uptake has been in cells that L. M.A. H.H. Williams D.L. does not SR-BI-mediated cholesterol or selective uptake of cholesteryl ester in two cell Scholar). in that HDL degradation was observed in cells that SR-BI, and not in cells that SR-BI and These results consistent with a requirement for CE to from the plasma membrane the CE concentration gradient for selective by transport of CE or endocytosis of is that the degradation of HDL with the internalization of This also a component to HDL-CE selective uptake D. Falstrault L. Brissette L. and of class B scavenger receptor in HepG2 1999; Scholar, G. Hobbs H.H. Scavenger receptor, class B, type of cholesterol by high density density and Biol. Chem. Scholar). data also support for that CE from HDL selective uptake to A. W.V. ester is from to as of a Biol. Chem. 2002; 277: Scholar, van der Westhuyzen D.R. class B, type I scavenger receptor the selective uptake of high density lipoprotein cholesterol into Biol. Chem. 1999; 274: Scholar). Although we did not in HDL and that was from HDL by selective uptake, we that the observed are not in HDL not with we have demonstrated in the cell model that SR-BI is required for HDL we that of is of from HDL. This of CE from the plasma membrane for In we demonstrate that in primary mouse hepatocytes, efficient CE selective uptake does not require endocytosis or recycling of HDL and that the HDL endocytosis is holoparticle uptake mediated by of HDL G. P. density lipoprotein protein contributes to selective uptake of high density lipoprotein cholesteryl esters by cells and primary Biol. Chem. 2001; 276: Scholar, S. T. of is A-I receptor in HDL Scholar). Although and SR-BI the efficiency of selective uptake, in and This is to the of and were for for with and and for critical of the This was supported by from the of to and to and by in and A-I caveolin-1 cholesteryl ester carboxyl ester lipase protein cholesteryl protein scavenger receptor class B type I protein

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