title: Cholesterol induces apoptosis-associated loss of the activated leukocyte cell adhesion molecule (ALCAM) in human monocytes.
abstract: The 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 μg/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.
authors: Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Germany.
authors: Stefan J
authors: SJ
authors: Rauch
authors: Anke C
authors: AC
authors: Rosenkranz
authors: Andreas
authors: A
authors: Böhm
authors: Jutta
authors: J
authors: Meyer-Kirchrath
authors: Thomas
authors: T
authors: Hohlfeld
authors: Karsten
authors: K
authors: Schrör
authors: Bernhard H
authors: BH
authors: Rauch
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D050197:Atherosclerosis / Q000473:pathology; D002465:Cell Movement; D002633:Chemotaxis; D002784:Cholesterol / Q000008:administration & dosage / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D009000:Monocytes / Q000378:metabolism*; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol