E-LDL upregulates TOSO expression and enhances the survival of human macrophages.
Uptake of modified lipoproteins by macrophages causes foam cell formation and promotes atherosclerosis. Atherogenic lipoproteins are cytotoxic and induce cell death under certain conditions but may also enhance macrophage survival. Macrophages treated with enzymatically modified LDL (E-LDL) were subjected to GeneChip analysis and the antiapoptotic gene TOSO was found induced. TOSO mRNA is upregulated and apoptosis is reduced in E-LDL but not in oxidized LDL (Ox-LDL) loaded macrophages. FLIP(L) abundance was suggested to mediate the antiapoptotic properties of TOSO; however, FLIP(L) was not changed. Ox-LDL is internalized predominantly by scavenger receptors such as CD36 while E-LDL particles are preferentially internalized by Fc- and complement-receptor dependent phagocytosis and internalization of phagobeads by macrophages upregulates TOSO. In COS-7 cells however, phagocytotic activity was not affected by TOSO. These data indicate that E-LDL-generated foam cells are protected from cell death most likely through the expression of TOSO by a FLIP(L) independent mechanism.
Sigruener
Alexander
A
Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Medical Center, Franz-Josef-Strauss Allee 11, D-93042 Regensburg, Germany.
Buechler
Christa
C
Bared
Salim Maa
SM
Grandl
Margot
M
Aslanidis
Charalampos
C
Ugocsai
Peter
P
Gehrmann
Mathias
M
Schmitz
Gerd
G
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D014357:Trypsin / Q000378:metabolism; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C505533:FADD protein, human; C112037:FCMR protein, human; D053200:Fas-Associated Death Domain Protein; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D014357:Trypsin