Anti-platelet drugs attenuate the expansion of circulating CD14highCD16+ monocytes under pro-inflammatory conditions

Cardiovasc Res. 2016 Jul 1;111(1):26-33. doi: 10.1093/cvr/cvw089. Epub 2016 Apr 26.

Abstract

Aims: Levels of circulating CD14(high)CD16(+) monocytes increase in atherosclerotic patients and are predictive of future cardiovascular events. Platelet activation has been identified as a crucial determinant in the acquisition of a CD16(+) phenotype by classical CD14(high)CD16(-) cells. We tested the hypothesis that anti-platelet drugs modulate the phenotype of circulating monocytes.

Methods and results: Sixty healthy subjects undergoing influenza immunization were randomly assigned to either no treatment or anti-platelet therapy, namely aspirin 300 mg or 75 mg daily, or clopidogrel (300 mg loading dose followed by 75 mg), for 48 h post-immunization (n = 15/group). Monocyte subsets, high-sensitivity C-reactive protein, pro-inflammatory cytokines, and P-selectin were measured at baseline and post-immunization. The CD14(high)CD16(+) monocyte cell count rose by 67.3% [interquartile range (IQR): 35.7/169.2; P = 0.0002 vs. baseline] in untreated participants. All anti-platelet regimes counteracted expansion of this monocytic subpopulation. Although no statistical differences were noted among the three treatments, aspirin 300 mg was the most efficacious compared with the untreated group (-12.5% change from baseline; IQR: -28.7/18.31; P = 0.001 vs. untreated). Similarly, the rise in P-selectin (17%; IQR: -5.0/39.7; P = 0.03 vs. baseline) observed in untreated participants was abolished by all treatments, with aspirin 300 mg exerting the strongest effect (-30.7%; IQR: -58.4/-0.03; P = 0.007 vs. untreated). Changes in P-selectin levels directly correlated with changes in CD14(high)CD16(+) cell count (r = 0.5; P = 0.0002). There was a similar increase among groups in high-sensitivity C-reactive protein (P < 0.03 vs. baseline levels).

Conclusions: Anti-platelet drugs exert an immunomodulatory action by counteracting CD14(high)CD16(+) monocyte increase under pro-inflammatory conditions, with this effect being dependent on the amplitude of P-selectin reduction.

Keywords: Aspirin; Clopidogrel; Inflammation; Monocytes; Platelets.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspirin / administration & dosage*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cell Proliferation / drug effects*
  • Clopidogrel
  • Cytokines / blood
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins / blood
  • Humans
  • Immunologic Factors / administration & dosage*
  • Inflammation / blood*
  • Inflammation / immunology
  • Inflammation Mediators / blood
  • Influenza Vaccines / administration & dosage*
  • Lipopolysaccharide Receptors / blood*
  • London
  • Male
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / metabolism
  • P-Selectin / blood
  • Phenotype
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Receptors, IgG / blood*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Vaccination

Substances

  • Biomarkers
  • Cytokines
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Immunologic Factors
  • Inflammation Mediators
  • Influenza Vaccines
  • Lipopolysaccharide Receptors
  • P-Selectin
  • Platelet Aggregation Inhibitors
  • Receptors, IgG
  • SELP protein, human
  • C-Reactive Protein
  • Clopidogrel
  • Ticlopidine
  • Aspirin