De novo expression of the class-A macrophage scavenger receptor conferring resistance to apoptosis in differentiated human THP-1 monocytic cells.
The class-A macrophage scavenger receptor (MSR) is a trimeric multifunctional protein expressed selectively in differentiated monomyeloid phagocytes which mediates uptake of chemically modified lipoproteins and bacterial products. This study investigated whether MSR plays a role in the regulation of apoptosis, a model of genetically programmed cell death. De novo expression of MSR occurred in human THP-1 monocytic cells differentiated with phorbol esters, which activated a nuclear transcription factor binding to the Ap1/ets-like domain of the MSR promoter. The phorbol ester-stimulated THP-1 cells also expressed increased levels of the pro-apoptotic gene products, caspase-3 and Fas ligand, but the cells exhibited no change in apoptosis. Global activation of GTP-binding proteins with fluoride anions triggered apoptosis of THP-1 cells in a time- and concentration-dependent manner, demonstrated by nuclear shrinkage and fragmentation and internucleosomal DNA fragmentation. However, the MSR-expressing THP-1 macrophage-like cells showed a significant reduction in apoptosis compared to undifferentiated control THP-1 cells, which produce MSR at undetectable levels. Fluoride stimulation also triggered apoptosis of human Jurkat T cells. Stimulation with phorbol ester made no difference in apoptosis between treated and untreated Jurkat cells. Finally, Chinese hamster ovary (CHO) cells overexpressing the class-A MSR type I by cDNA transfection showed markedly increased resistance to G-protein-coupled apoptosis. Thus, de novo expression of MSR associated with monocyte maturation into macrophages appears to confer the resistance of macrophages to apoptotic stimulation by G-protein activation.
Liao
H S
HS
Cardiovascular and Pulmonary Research Institute, Allegheny University of the Health Sciences, Pittsburgh, Pennsylvania 15212, USA.
Matsumoto
A
A
Itakura
H
H
Pittman
T
T
Kodama
T
T
Geng
Y J
YJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D016466:CHO Cells; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D053222:Fas Ligand Protein; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D018076:DNA, Complementary; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C495139:MSR1 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D005459:Fluorides