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



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).



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.
Department of Clinical Pharmacology, Cardiovascular Division, British Heart Foundation Centre for Research Excellence, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
Kerry
K
Layne
Department of Clinical Pharmacology, Cardiovascular Division, British Heart Foundation Centre for Research Excellence, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
Paolo
P
Di Giosia
Department of Clinical Pharmacology, Cardiovascular Division, British Heart Foundation Centre for Research Excellence, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
Albert
A
Ferro
Department of Clinical Pharmacology, Cardiovascular Division, British Heart Foundation Centre for Research Excellence, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK gabriella.passacquale@kcl.ac.uk.
Gabriella
G
Passacquale
D000328:Adult; D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D000077144:Clopidogrel; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007249:Inflammation / Q000097:blood* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage*; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008131:London; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019007:P-Selectin / Q000097:blood; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D017452:Receptors, IgG / Q000097:blood*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014611:Vaccination
D015415:Biomarkers; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007155:Immunologic Factors; D018836:Inflammation Mediators; D007252:Influenza Vaccines; D018950:Lipopolysaccharide Receptors; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D017452:Receptors, IgG; C546937:SELP protein, human; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
Aspirin; Clopidogrel; Inflammation; Monocytes; Platelets