Anti-platelet drugs attenuate the expansion of circulating CD14^highCD16⁺ monocytes under pro-inflammatory conditions

TY - JOUR

T1 - Anti-platelet drugs attenuate the expansion of circulating CD14highCD16+ monocytes under pro-inflammatory conditions

AU - Layne, Kerry

AU - Di Giosia, Paolo

AU - Ferro, Albert

AU - Passacquale, Gabriella

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Aims: Levels of circulating CD14highCD16+ 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 CD14highCD16- 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 CD14highCD16+ 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 (212.5% change from baseline; IQR: 228.7/18.31; P = 0.001 vs. untreated). Similarly, the rise in P-selectin (17%; IQR: 25.0/39.7; P = 0.03 vs. baseline) observed in untreated participants was abolished by all treatments, with aspirin 300 mg exerting the strongest effect (230.7%; IQR: 258.4/20.03; P = 0.007 vs. untreated). Changes in P-selectin levels directly correlated with changes in CD14highCD16+ 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 CD14highCD16+ monocyte increase under pro-inflammatory conditions, with this effect being dependent on the amplitude of P-selectin reduction.

AB - Aims: Levels of circulating CD14highCD16+ 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 CD14highCD16- 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 CD14highCD16+ 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 (212.5% change from baseline; IQR: 228.7/18.31; P = 0.001 vs. untreated). Similarly, the rise in P-selectin (17%; IQR: 25.0/39.7; P = 0.03 vs. baseline) observed in untreated participants was abolished by all treatments, with aspirin 300 mg exerting the strongest effect (230.7%; IQR: 258.4/20.03; P = 0.007 vs. untreated). Changes in P-selectin levels directly correlated with changes in CD14highCD16+ 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 CD14highCD16+ monocyte increase under pro-inflammatory conditions, with this effect being dependent on the amplitude of P-selectin reduction.

KW - Aspirin

KW - Clopidogrel

KW - Inflammation

KW - Monocytes

KW - Platelets

UR - http://www.scopus.com/inward/record.url?scp=85007138018&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvw089

DO - 10.1093/cvr/cvw089

M3 - Article

C2 - 27118470

AN - SCOPUS:85007138018

SN - 0008-6363

VL - 111

SP - 26

EP - 33

JO - Cardiovascular Research

JF - Cardiovascular Research

IS - 1

ER -