The CD14++CD16+ monocyte subset and monocyte-platelet interactions in patients with ST-elevation myocardial infarction.
OBJECTIVE
Monocytes contribute to both myocardial damage and repair by virtue of subset heterogeneity. The dynamics and functional characteristics of the three human monocyte subsets, including the unique CD14++CD16+ subset, and their contributions to monocyte platelet aggregates (MPAs) following ST-elevation myocardial infarction (STEMI) are unknown. We aimed to examine dynamic changes and relation to left ventricular ejection fraction (LVEF) of the three human monocyte subsets and their aggregates with platelets following STEMI.


METHODS
Three monocyte subsets, CD14++CD16-CCR2+ ('classical', Mon1), CD14++CD16+CCR2+ ('intermediate', Mon2) and CD14+CD16++CCR2- ('non-classical', Mon3), and their contribution to MPAs were analyzed by flow cytometry in 50 patients with STEMI, 40 patients with stable coronary artery disease (CAD) and 40 healthy volunteers. Study parameters were measured within 24 h of primary percutaneous coronary intervention (PCI) (day1) and on days 3, 7 and 30. Monocyte activation was assessed by measuring the nuclear factor κB (NFκB) pathway. LVEF was assessed 6 weeks after STEMI. Correlations between monocyte subsets/MPAs and plasma cytokines and troponin were assessed.


RESULTS
We observed marked differences in subset dynamics, with a prominent increase in Mon2 (P < 0.0001) but no changes in Mon3. Significant increases in Mon2 CD14 (P = 0.002) and CCR2 (P < 0.0001) expression, and reduction in CD16 expression (P = 0.001) were seen. NFκB pathway activity increased most prominently in Mon2 (P = 0.007). Mon2 count correlated with peak troponin (r = 0.31, P = 0.04) and plasma interleukin (IL)-6 (r = 0.65, P < 0.0001) and IL-10 (r = 0.34, P = 0.017). Mon1 correlated with IL-6 (r = 0.55, P < 0.0001). Reduced Mon2 expression of CD16 on day 1 was independently predictive of higher LVEF (β = -0.37, P = 0.013). The increase in MPA count following STEMI persisted at 1 month.


CONCLUSIONS
The Mon2 'intermediate' subset has unique dynamic and functional characteristics following STEMI and significant correlations with troponin, plasma cytokines and convalescent left ventricular function. The persistent increase in MPA count 30 days after STEMI may affect monocyte subset functional activity.
University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK.
L D
LD
Tapp
E
E
Shantsila
B J
BJ
Wrigley
B
B
Pamukcu
G Y H
GY
Lip
D000368:Aged; D001792:Blood Platelets / Q000473:pathology*; D002449:Cell Aggregation; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood; D004562:Electrocardiography; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D009203:Myocardial Infarction / Q000276:immunology* / Q000503:physiopathology; D017452:Receptors, IgG / Q000276:immunology*
D018932:Chemokine CCL2; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG