title: Receptors to interleukin-6 and adhesion molecules on circulating monocyte subsets in acute myocardial infarction.
abstract: The role of individual monocyte subsets in inflammation and recovery post-myocardial infarction (MI) is insufficiently understood. It was the objective of this study to evaluate the dynamics of monocyte expression of receptors to vascular cell adhesion molecule (VCAM-1r), intercellular adhesion molecule (ICAM-1r), and interleukin-6 (IL-6r) following MI and their relation to inflammatory cytokines, fibrinolytic factors and annexin V-binding microparticles. Expression of VCAM-1r, ICAM-1r, IL-6r on CD14++CD16-(Mon1), CD14++CD16+(Mon2), CD14+CD16++(Mon3) monocyte subsets were quantified by flow cytometry in patients with ST-elevation MI (STEMI, n=50), non-STEMI (n=48) and stable coronary artery disease (n=40). In STEMI, parameters were measured on days 1, 3, 7, 30. On admission with STEMI, VCAM-1r expression was reduced on Mon1 (p=0.007), Mon2 (p=0.036), Mon3 (p=0.005), whilst in NSTEMI there was significant up-regulation of expression by Mon2 (p=0.024) and Mon3 (p=0.049). VCAM-1r on Mon1 correlated positively with plasma IL-1β levels (p=0.001). IL-6r was reduced on Mon2 in acute STEMI, with upregulation of the receptor on Mon1 and Mon2 during follow-up. IL-6r density correlated negatively with plasma levels of tissue-type plasminogen activator (p=0.0005 for Mon1, p=0.001 for Mon2 and Mon3), and positively with annexin V-binding microparticles (p=0.03 for Mon1, p=0.005 for Mon2 and p=0.005 for Mon3). There was no change in monocyte ICAM-1r expression. In conclusion, expression of IL-6r and VCAM-1r is reduced on circulating monocyte subsets involved in inflammatory responses in STEMI. This may represent a regulatory feed-back mechanism aiming to re-balance the marked inflammation which is typically present following acute MI or selective homing of monocytes with high receptor expression to damaged myocardium.
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK. g.y.h.lip@bham.ac.uk
authors.forename: Eduard
authors.initials: E
authors.lastname: Shantsila
authors.forename: Luke D
authors.initials: LD
authors.lastname: Tapp
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Wrigley
authors.forename: Silvia
authors.initials: S
authors.lastname: Montoro-García
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D017304:Annexin A5 / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification* / Q000276:immunology*; D009203:Myocardial Infarction / Q000097:blood* / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000097:blood*; D019947:Receptors, Interleukin-6 / Q000097:blood*; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D017304:Annexin A5; D016207:Cytokines; C573420:ICAM1 protein, human; C508603:IL6R protein, human; D018836:Inflammation Mediators; D011956:Receptors, Cell Surface; D019947:Receptors, Interleukin-6; D019714:Tissue Inhibitor of Metalloproteinases; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1