Enhancement of monocyte adhesion to endothelial cells by oxidatively modified low-density lipoprotein is mediated by activation of CD11b.
Treatment of human peripheral blood monocytes with oxidized (oxLDL), minimally modified low-density lipoprotein (mmLDL) or lysophosphatidylcholine (LPC) for 24h was associated with macrophage-like differentiation, as assessed by morphology/CD14 expression. Suppression of these effects by staurosporin (STS) indicated the dependence on protein kinase C (PKC) activation. OxLDL and mmLDL increased monocyte adhesion to human umbilical vein endothelial cells 2-fold. Enhancement of adhesion was prevented by an anti-CD11b mAb, demonstrating the involvement of CD11b. While LPC increased monocyte adhesion, inhibition of PKC by STS reversed enhancement of adhesion by oxLDL, showing mediation by LPC-induced PKC activation. OxLDL, mmLDL or LPC increased CD11b expression and stimulated a distinct peak in fluorescence intensity, suggesting that CD11b activation was crucial for enhanced monocyte adhesion.
Weber
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Institut für Prophylaxe der Kreislaufkrankheiten, München, Germany.
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Weber
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D000470:Alkaloids / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000502:physiology*; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D019311:Staurosporine; D014471:Umbilical Veins
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D008077:Lipoproteins, LDL; D016177:Macrophage-1 Antigen; D011493:Protein Kinase C; D019311:Staurosporine