High-density lipoprotein inhibits the uptake of modified low- density lipoprotein and the expression of CD36 and FcgammaRI.
OBJECTIVE
Modified low-density lipoprotein (mLDL), mainly upon oxidative and enzymatic modification, is the major atherogenic lipoprotein. Conversely, high-density lipoprotein (HDL) is considered antiatherogenic because of its ability to remove cholesterol. The aim of this work was to analyze both the influence of HDL on the uptake of mLDL and the expression of CD36 and Fcgamma I receptors on monocytic cell lines during cell differentiation.


METHODS
Uptake of fluorescein isothiocyanate (FITC)-conjugated LDL and FITC-conjugated mLDL, i.e., copper-oxidized LDL (oxLDL) or trypsin enzyme modified LDL (enzLDL), was analyzed, as well as the expression of CD36 and FcgammaRI in THP-1 and U937 cells, using flow cytometry.


RESULTS
HDL inhibited the uptake of mLDL, which varied in degree depending on the cell line or type of mLDL. Further, HDL rapidly decreased CD36 and FcgammaRI involved in the uptake of mLDL.


CONCLUSIONS
We demonstrate that modified LDL promotes specific LDL receptor-independent uptake by monocytic cell lines, and that the uptake of LDL and enzLDL is less than that of oxLDL. In this process, HDL diminishes the uptake of LDL or mLDL, which may involve the down-regulation of receptors (CD36 and Fcgamma I). This regulatory process represents another way by which HDL can be anti-atherogenic and it depends on the type of modification of LDL and the stage of differentiation of monocytes to macrophages.
Carvalho
Márcia Dias Teixeira
MD
Laboratório de Imunofisiopatologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil. mdias@usp.br
Vendrame
Célia Maria Vieira
CM
Ketelhuth
Daniel Francisco Jacon
DF
Yamashiro-Kanashiro
Edite Hatsumi
EH
Goto
Hiro
H
Gidlund
Magnus
M
D018955:CD36 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D015151:Immunoblotting; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000494:pharmacology
D018955:CD36 Antigens; C489017:FCGR1A protein, human; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D017452:Receptors, IgG; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein