The ATP Binding Cassette Transporter A1 Contributes to the Secretion of Interleukin 1β 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-1β from monocytes and macrophages. We investigated the contribution of ABCA1 to IL-1β 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-1β from full blood or freshly isolated monocytes. By contrast, anti-ABCA1 antisense oligonucleotides decreased the LPS-induced secretion of IL-1β from macrophages by 30–50%. The secretion of the precursor pro-IL-1β and TNFα was not inhibited. Compared to normal macrophages, LPS-stimulated Tangier disease macrophages secreted less IL-1β relative to TNFα. Also the spontaneous secretion of IL-1β by Tangier macrophages was lower than by control cells. We conclude that IL-1β is secreted from monocytes by an ABCA1-independent pathway and from macrophages by ABCA1-dependent and -independent pathways.