CX3CR1 receptor is up-regulated in monocytes of coronary artery diseased patients: impact of pre-inflammatory stimuli and renin-angiotensin system modulators

Thromb Res. 2007;121(3):387-95. doi: 10.1016/j.thromres.2007.04.005. Epub 2007 May 23.

Abstract

Fractalkine/CX3CR1 pathway is considered a major modulator of atherosclerosis. In the present study, expression of CX3CR1 on PBMCs/monocytes of healthy individuals and coronary artery diseased patients was initially assessed by flow cytometry. Effects of pre-inflammatory cytokines interferon (INF)-gamma and tumor necrosis factor (TNF)-alpha on expression of CX3CR1 and a single representative of each major chemokine family (CCR5 and CXCR4) were further assessed in three cell models: THP-1 monocytes, Jurkat T lymphocytes and primary monocytes isolated from healthy donors. Finally, effects of angiotensin-converting enzyme (ACE) inhibitors captopril, lisinopril and angiotensin receptor blocker (ARB) losartan on chemokine receptor expression were evaluated in the same cell models either in a naive or stimulated state. INF-gamma significantly affected the chemokine receptor phenotype of THP-1 cells by increasing the rate of CX3CR1-positive cells. Pre-treatment with the ACE inhibitors, captopril and lisinopril, and the ARB, losartan, did not influence these effects. Captopril and lisinopril similarly had no effect on either stimulated or naive primary monocytes. Yet, a small but repeatable increase in CX3CR1 expression after treatment with losartan was noted. Nevertheless, the latter observation did not retain statistical significance after applying the Bonferroni correction. In conclusion, our data did not indicate any significant effect of the ACE inhibitors on the chemokine receptor phenotype of monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • CX3C Chemokine Receptor 1
  • Captopril / pharmacology
  • Case-Control Studies
  • Cell Line
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / immunology*
  • Female
  • Humans
  • In Vitro Techniques
  • Inflammation Mediators / pharmacology
  • Interferon-gamma / pharmacology
  • Jurkat Cells
  • Lisinopril / pharmacology
  • Losartan / pharmacology
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Receptors, Chemokine / blood*
  • Receptors, Chemokine / metabolism
  • Recombinant Proteins
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / immunology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation / drug effects

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • Inflammation Mediators
  • Receptors, Chemokine
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Captopril
  • Lisinopril
  • Losartan