LDL activates signaling pathways leading to an increase in cytosolic free calcium and stimulation of CD11b expression in monocytes.
In the present study, we investigated the mechanisms by which plasma lipoproteins modulate the integrin-dependent adhesion properties of monocytes. LDL induced the expression of the monocyte CD11b in vitro as well as in vivo via intracellular signaling mechanisms involving calcium transients. The effect on CD11b transcription was specific for native LDL and was blocked by a neutralizing anti-LDL receptor antibody. Neither oxidized LDL nor HDL had any effect on CD11b expression. Although LDL stimulated CD11b surface expression, the integrins were not activated. To initiate the CD11b-specific adhesion to the endothelium, the engagement of chemokine receptor CCR2 and intact chemokine-to-integrin signaling was necessary. However, the activation of CCR2 with monocyte chemoattractant protein-1 not only stimulated the integrins preexisting on the cell surface, but also increased the number of CD11b molecules on the cell surface. This was particularly pronounced in THP-1 cells after treatment with LDL. In a previous study, we showed that LDL induces the expression of CCR2 in monocytes. We conclude that this may be the underlying cause of the enhanced chemokine effect on CD11b expression and activation observed with these cells.
Han
Ki Hoon
KH
Department of Medicine, University of California-San Diego, La Jolla, CA 92093, USA.
Chen
Yiming
Y
Chang
Mi Kyung
MK
Han
Yoon Chan
YC
Park
Jae-Hyung
JH
Green
Simone R
SR
Boullier
Agnès
A
Quehenberger
Oswald
O
D000818:Animals; D040881:CD11a Antigen / Q000096:biosynthesis; D039481:CD11b Antigen / Q000096:biosynthesis*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D039441:Integrin alpha4 / Q000096:biosynthesis; D016023:Integrins / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
C515334:CCR2 protein, human; D040881:CD11a Antigen; D039481:CD11b Antigen; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D016023:Integrins; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C099252:oxidized low density lipoprotein; D039441:Integrin alpha4; D010100:Oxygen; D002118:Calcium