High-density lipoprotein reduces the human monocyte inflammatory response.

Abstract

OBJECTIVE:

Whereas the anti-inflammatory effects of high-density lipoprotein (HDL) on endothelial cells are well described, such effects on monocytes are less studied.

METHODS AND RESULTS:

Human monocytes were isolated from whole blood followed by assessment of CD11b activation/expression and cell adhesion under shear-flow. HDL caused a dose-dependent reduction in the activation of CD11b induced by PMA or receptor-dependent agonists. The constituent of HDL responsible for the antiinflammatory effects on CD11b activation was found to be apolipoprotein A-I (apoA-I). Cyclodextrin, but not cyclodextrin/cholesterol complex, also inhibited PMA-induced CD11b activation implicating cholesterol efflux as the main mechanism. This was further confirmed with the demonstration that cholesterol content of lipid rafts diminished after treatment with the cholesterol acceptors. Blocking ABCA1 with an anti-ABCA1 antibody abolished the effect of apoA-I. Furthermore, monocytes derived from a Tangier disease patient definitively confirmed the requirement of ABCA1 in apoA-I-mediated CD11b inhibition. The antiinflammatory effects of apoA-I were also observed in functional models including cell adhesion to an endothelial cell monolayer, monocytic spreading under shear flow, and transmigration.

CONCLUSIONS:

HDL and apoA-I exhibit an antiinflammatory effect on human monocytes by inhibiting activation of CD11b. ApoA-I acts through ABCA1, whereas HDL may act through several receptors.

• Authors: Andrew J Murphy, Kevin J Woollard, Anh Hoang, Nigora Mukhamedova, Roslynn A Stirzaker, Sally P A McCormick, Alan T Remaley, Dmitri Sviridov, Jaye Chin-Dusting
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 28 Issue 11 Pg. 2071-7 (Nov 2008) ISSN: 1524-4636 [Electronic] United States
• PMID: 18617650 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCA1 protein, human
• ATP Binding Cassette Transporter 1
• ATP-Binding Cassette Transporters
• Actins
• Apolipoprotein A-I
• CD11b Antigen
• Cyclodextrins
• ITGAM protein, human
• Lipoproteins, HDL
• SCARB1 protein, human
• Scavenger Receptors, Class B
• Cholesterol
• Tetradecanoylphorbol Acetate

Topics

• ATP Binding Cassette Transporter 1
• ATP-Binding Cassette Transporters (metabolism)
• Actins (metabolism)
• Apolipoprotein A-I (metabolism)
• Atherosclerosis (metabolism, pathology, prevention & control)
• CD11b Antigen (metabolism)
• Cell Adhesion
• Cell Shape
• Cells, Cultured
• Cholesterol (deficiency, metabolism)
• Cyclodextrins (pharmacology)
• Endothelial Cells (metabolism)
• Humans
• Inflammation (metabolism, pathology, prevention & control)
• Lipoproteins, HDL (metabolism)
• Membrane Microdomains (metabolism)
• Monocytes (drug effects, metabolism, pathology)
• Platelet Adhesiveness
• Scavenger Receptors, Class B
• Stress, Mechanical
• Tangier Disease (metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Time Factors