LDL activates signaling pathways leading to an increase in cytosolic free calcium and stimulation of CD11b expression in monocytes

Abstract

In the present study, we investigated the mechanisms by which plasma lipoproteins modulate the integrindependent 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

Overexpression of Uncoupling Protein 2 in THP1 Monocytes Inhibits β2Integrin-Mediated Firm Adhesion and Transendothelial Migration

“…We previously reported that CD11b-dependent firm adhesion was required for transendothelial migration of monocytes in response to MCP-1. 5 Although UCP2 overexpression did not affect surface expression of CCR2, the receptor for MCP-1, the resulted CD11b reduction profoundly inhibited MCP-1-mediated transendothelial migration in this study. The positive correlation between CD11b expression in circulating monocytes and the degree of monocyte infiltration into the proatherogenic vascular wall has been documented.…”

“…5 Complete sequence of human UCP2 was amplified, inserted into the expression vector pcDNA3.1(Invitrogen), and confirmed by DNA sequencing. L-␣-phosphatidylcholine (ePC), L-␣-phosphatidylserine (bPS), 1,2-Dioleoyl-sn-Glycero-3-phosphoethanolamine (DOPE), and sphingomyelin (eSph) and cholesterol (Chol) (Avanti Polar Lipids, Alabaster, AL) in chloroform, were mixed in an approximate weight ratio of ePC:DOPE:eSph:Chol:bPSϭ1.6:3:1.47:3:1.3 (10.37 mg/mL), filtered (0.2 m pore size), dried in a N 2 -filled rotary evaporator to make a thin film, and mixed with 200 g UCP2-pcDNA3.1 (1 g/L stock).…”

“…4 Monocytes express CC chemokine receptor 2 (CCR2), which binds monocyte chemoattractant protein-1 (MCP-1), leading to ␤ integrin-mediated firm adhesion and subsequent transmigration of adhered monocytes through the vascular endothelium. 5 Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family, and is ubiquitously expressed in various tissues and by monocytes and macrophages. UCP2 is located on the mitochondrial inner membrane.…”

Role of Junctional Adhesion Molecule-Like Protein in Mediating Monocyte Transendothelial Migration

“…21 THP-1 monocytes (China Cell Culture Center, Shanghai, China) were cultured and maintained as described. 22 Immortalized HMEC-1 was kindly provided by Dr E.W. Ades (Centers for Disease Control and Prevention, Atlanta, Ga).…”

Effects of Native and Modified Low-Density Lipoproteins on Monocyte Recruitment in Atherosclerosis

“…89 Similarly, LDL induced CD11b in human monocytes resulting in CD11b-dependent adhesion to endothelial monolayers, however only after stimulation with CCL2. 115 …”