Inhibitory effects of N-acetylcysteine on scavenger receptor class A expression in human macrophages.
OBJECTIVE
The formation of foam cells from monocyte-derived macrophages involves the uptake of modified lipoproteins by scavenger receptors. Antioxidants inhibit lipoprotein oxidation and may also modulate gene expression. We investigated the effect of the antioxidant N-acetylcysteine on the expression of the class A scavenger receptor (SR-A) types I and II in human macrophages.


METHODS
Monocytes and macrophages from healthy blood donors and plaque-derived macrophages from patients undergoing carotid endarterectomy were used for experiments. SR-A mRNA was analysed with quantitative and semiquantitative reverse transcription-polymerase chain reaction, and ligand binding and uptake were assessed with 125I-labelled acetylated low-density lipoprotein (LDL).


RESULTS
Incubation of monocytes and monocyte-derived macrophages with N-acetylcysteine decreased both SR-A I and II mRNA expression. N-Acetylcysteine also reduced SR-A mRNA in lesion-derived cells. Binding and uptake of 125I-acetylated LDL was decreased after brief incubation with N-acetylcysteine. After longer periods of incubation with N-acetylcysteine we observed an increased degradation of lipoproteins.


CONCLUSIONS
Our results imply that N-acetylcysteine leads to a decrease in SR-A mRNA and initially also to an attenuated uptake of modified lipoproteins. This adds more to the knowledge about the cellular actions of this drug.
Svensson
L
L
Wallenberg Laboratory, The Cardiovascular Institute, The Sahlgrenska Academy at Göteborg University, Sweden.
Norén
K
K
Wiklund
O
O
Lindmark
H
H
Ohlsson
B
B
Hultén
L Mattsson
LM
D000111:Acetylcysteine / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D005978:Glutathione / Q000032:analysis; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A
D015815:Cell Adhesion Molecules; C495139:MSR1 protein, human; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D005978:Glutathione; D000111:Acetylcysteine