| Free cholesterol alters macrophage morphology and mobility by an ABCA1 dependent mechanism. | |
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MedLine Citation:
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PMID: 21215399 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: To investigate whether the morphological and functional changes typical of cell immobilization induced by free cholesterol (FC) accumulation in macrophages is related to the activity of the ATP-binding cassette transporter (ABCA1). METHODS AND RESULTS: FC loading induced actin rearrangement with ruffling and cell spreading in macrophages that normally express ABCA1, but to a significant lesser extent in ABCA1-KO mouse peritoneal macrophages (MPMs) and in normal cells upon pharmacological inhibition of ABCA1 with probucol. In ABCA1-KO MPMs and in probucol-treated J774 cell migration was inhibited to a lower extent by FC as compared to control cells. Similar results were found in stably ABCA1 knocked down J774 (ABCA1-KD-J774) obtained by RNA interference. FC accessible to cholesterol oxidase, a measure of plasma membrane FC content, was significantly higher in FC-loaded WT MPMs and control J774 than in FC-loaded ABCA1-KO MPMs, ABCA1-KD-J774 or probucol-treated J774. In parallel plasma membrane total phospholids and sphingomyelin increased after cholesterol loading in control J774 but not in ABCA1-KD-J774. In addition, apoA-I, that removes FC from ABCA1 specific pool, partially restored chemotactic response in FC-loaded control J774. No effect was observed with HDL(2) that does not interact with ABCA1. Finally, FC-induced Rac activation was more efficient in control J774 than in ABCA1-KD-J774. and was prevented by probucol and apoA-I in control J774. CONCLUSION: In macrophages ABCA1 activity mediates FC ability to alter plasma membrane organization, to inhibit cell migration, and to activate a Rac-mediated signaling pathway. |
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Authors:
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Maria Pia Adorni; Elda Favari; Nicoletta Ronda; Agnese Granata; Stefano Bellosta; Lorenzo Arnaboldi; Alberto Corsini; Rita Gatti; Franco Bernini |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-12-15 |
Journal Detail:
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Title: Atherosclerosis Volume: - ISSN: 1879-1484 ISO Abbreviation: - Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2011-1-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0242543 Medline TA: Atherosclerosis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Pharmacological and Biological Sciences, and Applied Chemistries, Parco Area delle Scienze 27/A, 43124 Parma, University of Parma, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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