Expression of the ATP-binding cassette transporter gene ABCG1 (ABC8) in Tangier disease.
Several members of the ATP-binding cassette (ABC) transporter family are involved in cholesterol efflux from cells. A defect in one member, ABCA1, results in Tangier disease, a condition characterized by cholesterol accumulation in macrophages and virtual absence of mature circulating high-density lipoproteins. Expression of a second member, ABCG1, is increased by cholesterol-loading in human macrophages. We now show that ABCG1, which we identified by differential display RT-PCR in foamy macrophages, is overexpressed in macrophages from patients with Tangier disease compared to control macrophages. On examination by confocal laser scanning microscopy, ABCG1 was present in perinuclear structures within the cell. In addition, a combination of in situ hybridization and indirect immunofluorescence microscopy revealed that ABCG1 is expressed in foamy macrophages within the atherosclerotic plaque. These data indicate that not only ABCA1 but also ABCG1 may play a role in the cholesterol metabolism of macrophages in vitro and in the atherosclerotic plaque.
Lorkowski
S
S
Institute of Arteriosclerosis Research, University of Münster, Münster, Germany.
Kratz
M
M
Wenner
C
C
Schmidt
R
R
Weitkamp
B
B
Fobker
M
M
Reinhardt
J
J
Rauterberg
J
J
Galinski
E A
EA
Cullen
P
P
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013631:Tangier Disease / Q000235:genetics*
C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol