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pubmed-article:21440089pubmed:abstractTextThe activated leukocyte cell adhesion molecule (ALCAM/CD166) is associated with cell migration and leukocyte invasion into the vessel wall. This study investigates the impact of cholesterol loading on the expression of ALCAM, as compared with P-selectin glycoprotein ligand-1 (PSGL-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in monocytic U937 cells and human primary monocytes. Cells were enriched with cholesterol by incubation with a cyclodextrin-cholesterol complex. Expression of adhesion molecules and apoptosis was determined by flow cytometry. Migration was quantified by chemotaxis toward serum. Incubation with cholesterol (10-100 ?g/ml) for 16 h caused a concentration-dependent increase in apoptosis. Enhanced apoptosis was associated with reduction of ALCAM by >70%. While PSGL-1 was affected similarly, expression of VCAM-1 was markedly increased by cholesterol and ICAM-1 levels were not regulated. The nonselective caspase/apoptosis inhibitor Q-VD-OPh partially prevented cholesterol-modulated alteration of adhesion molecule expression. Migration of cholesterol-rich monocytic cells toward serum was greatly reduced. This effect was partially restored by Q-VD-OPh and was dependent on ALCAM as shown by ALCAM-neutralizing antibodies. In conclusion, cholesterol-induced apoptosis in monocytes is accompanied by reduced expression of ALCAM and attenuated monocyte migration. This may restrain monocytes at cholesterol-rich sites and thereby expedite vascular lesion formation.lld:pubmed
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pubmed-article:21440089pubmed:authorpubmed-author:RauchStefan...lld:pubmed
pubmed-article:21440089pubmed:copyrightInfoCopyright © 2011 Elsevier Inc. All rights reserved.lld:pubmed
pubmed-article:21440089pubmed:issnTypeElectroniclld:pubmed
pubmed-article:21440089pubmed:volume54lld:pubmed
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pubmed-article:21440089pubmed:articleTitleCholesterol induces apoptosis-associated loss of the activated leukocyte cell adhesion molecule (ALCAM) in human monocytes.lld:pubmed
pubmed-article:21440089pubmed:affiliationInstitut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Germany.lld:pubmed
pubmed-article:21440089pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:21440089pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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