期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 42, 期 9, 页码 1562-1570出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2010.06.009
关键词
Acute phase proteins; Lipid rafts; Cholesterol; SERPINA1; Inflammation
资金
- Swedish Research Council, Hannover Medical School and National Institutes of Health of United States [R21AI068432, R01AT004148]
- Cambridge NIHR Biomedical Research Centre
Cholesterol is the most abundant lipid component of the plasma membrane, and thus the equilibrium between free cholesterol and raft cholesterol act as a determinant of raft function and cell signalling. The mechanisms that regulate the lipid raft cholesterol levels are largely unknown. Here we demonstrate that SERPINA1 (alpha 1-antitrypsin), an acute phase protein and the classical neutrophil elastase inhibitor, is localized within lipid rafts in primary human monocytes in vitro. SERPINA1 association with monocytes is inhibited by cholesterol depleting/efflux-stimulating agents (nystatin, filipin, M beta CD (methyl-betacyclodextrin) and oxidized low-density lipoprotein (oxLDL) and conversely, enhanced by free cholesterol. Furthermore, SERPINA1/monocyte association per se depletes lipid raft cholesterol as characterized by the activation of extracellular signal-regulated kinase 2, formation of cytosolic lipid droplets, and a complete inhibition of oxLDL uptake by monocytes. Our findings for the first time highlight that the entry and cell association of SERPINA1 is dependent on lipid raft cholesterol and that SERPINA1 depletes lipid raft cholesterol. (C) 2010 Elsevier Ltd. All rights reserved.
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