Different mechanisms of adhesion molecule expression in human dermal microvascular endothelial cells by xanthoma tissue-mediated and copper-mediated oxidized low density lipoproteins.
BACKGROUND
Oxidation of low density lipoprotein (LDL) has been implicated in infiltration of foam cells derived from circulating monocytes. Monocyte adhesion to endothelial cells and migration into dermis are essential steps for infiltration of foam cells.


OBJECTIVE
We investigated the role of adhesion molecules contributing to the process of monocyte adhesion to human dermal microvascular endothelial cells (HDMEC). Special attention was paid to the signal transduction for adhesion molecule expression induced by two distinct types of oxidized LDL.


METHODS
HDMEC were incubated with xanthoma tissue-modified LDL (x-LDL), a model of extravasated LDL oxidized in xanthoma lesions, or Cu(2+)-treated LDL (Cu-LDL), a model of oxidized LDL. Adhesion of U937 cells, a human monocytic leukemia cell line, to HDMEC and expression of endothelial cell adhesion molecules on HDMEC were examined. Signal transduction pathways for the adhesion molecule expression were evaluated by employing specific inhibitors.


RESULTS
x-LDL induced adhesion of U937 cells to HDMEC through vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by activating tyrosine kinase pathway. Cu-LDL up-regulated the adhesion through not only VCAM-1 and E-selectin but also intercellular cell adhesion molecule-1 (ICAM-1) by activating G(i) protein pathway.


CONCLUSIONS
Extravasated and oxidized LDL in xanthoma lesions contributes to foam cell recruitment by activating tyrosine kinase pathway and inducing adhesion of monocytes to HDMEC through VCAM-1 and E-selectin. Cu-LDL, on the other hand, activates G(i) protein pathway and induces the adhesion through ICAM-1, VCAM-1 and E-selectin.
Matsumoto
Masaaki
M
Department of Dermatology, Kochi Medical School, Okohcho, Nankoku, Kochi 783-8505, Japan. matsumo@kochi-ms.ac.jp
Ikeda
Mitsunori
M
Seike
Masahiro
M
Kodama
Hajime
H
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008833:Microcirculation; D012867:Skin / Q000098:blood supply*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014973:Xanthomatosis / Q000378:metabolism* / Q000473:pathology
D015815:Cell Adhesion Molecules; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D003300:Copper