title: The ATP binding cassette transporter A1 contributes to the secretion of interleukin 1beta from macrophages but not from monocytes.
abstract: Deficiency of ABCA1 causes high density lipoprotein deficiency and macrophage foam cell formation in Tangier disease. ABCA1 was also postulated to mediate the secretion of IL-1beta from monocytes and macrophages. We investigated the contribution of ABCA1 to IL-1beta secretion from human monocytes and macrophages of normal donors and Tangier disease patients. Neither an anti-ABCA1 antisense oligonucleotide nor ABCA1 deficiency interfered with LPS-induced secretion of IL-1beta from full blood or freshly isolated monocytes. By contrast, anti-ABCA1 antisense oligonucleotides decreased the LPS-induced secretion of IL-beta from macrophages by 30-50%. The secretion of the precursor pro-IL-1beta and TNFalpha was not inhibited. Compared to normal macrophages, LPS-stimulated Tangier disease macrophages secreted less IL-1beta relative to TNFalpha. Also the spontaneous secretion of IL-1beta by Tangier macrophages was lower than by control cells. We conclude that IL-1beta is secreted from monocytes by an ABCA1-independent pathway and from macrophages by ABCA1-dependent and -independent pathways.
authors.affiliation: Institute of Arteriosclerosis Research, Domagkstrasse 3, Münster, D-48149, Germany.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhou
authors.forename: Thomas
authors.initials: T
authors.lastname: Engel
authors.forename: Christian
authors.initials: C
authors.lastname: Goepfert
authors.forename: Michael
authors.initials: M
authors.lastname: Erren
authors.forename: Gerd
authors.initials: G
authors.lastname: Assmann
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D013631:Tangier Disease / Q000097:blood
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger