Receptors to interleukin-6 and adhesion molecules on circulating monocyte subsets in acute myocardial infarction

2013 ◽  
Vol 110 (08) ◽  
pp. 340-348 ◽  
Author(s):  
Benjami Wrigley ◽  
Silvia Montoro-Garcia ◽  
Eduard Shantsila ◽  
Luke Tapp ◽  
Gregory Lip
Keyword(s):  
Myocardial Infarction ◽  
Adhesion Molecule ◽  
Interleukin 6 ◽  
Inflammatory Responses ◽  
Stable Coronary Artery Disease ◽  
Annexin V ◽  
Receptor Expression ◽  
Tissue Type ◽  
Intercellular Adhesion Molecule ◽  
Monocyte Subsets

SummaryThe 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.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.

CXCR4 positive and angiogenic monocytes in myocardial infarction

2013 ◽  
Vol 109 (02) ◽  
pp. 255-262 ◽  
Author(s):  
Benjamin Wrigley ◽  
Silvia Montoro-Garcia ◽  
Gregory Lip ◽  
Eduard Shantsila ◽  
Luke Tapp
Keyword(s):  
Myocardial Infarction ◽  
Stable Coronary Artery Disease ◽  
Scavenger Receptor ◽  
Tissue Type ◽  
Monocyte Subsets ◽  
Angiogenic Potential ◽  
Type Plasminogen Activator ◽  
Artery Disease ◽  
Stable Cad

SummaryLimited data are available on the role of monocytes in cardiac repair. In the present study, we evaluated the dynamic alterations of monocytes with reparative and angiogenic potential in patients with myocardial infarction(MI). Reparative CXCR4+ monocytes, and CD34+ and KDR+ monocytes with angiogenic potential derived from individual monocyte subsets were quantified by flow cytometry in patients with ST-elevation MI (n=50) and stable coronary artery disease (CAD, n=40). Parameters were measured on days 1, 3, 7 and 30 post MI. Monocyte subsets were defined as CD14++CD16–CCR2+ (‘classical’, Mon1), CD14++CD16+CCR2+ (‘intermediate’, Mon2), CD14+CD16++CCR2– (‘non-classical’, Mon3). Plasma levels of inflammatory cytokines, fibrinolytic factors and microparticles (MPs) were assessed on day 1. CXCR4+ and KDR+ monocytes were increased following MI, being more prominently associated with Mon2 (median[IQR] of CXCR4+ Mon2 60[25–126] per μl in STEMI vs. 27[21–41] per μl in stable CAD). The counts of CXCR4+ Mon2 in STEMI significantly reduced by day 30 of follow-up (27[18–47], p<0.001). Expression of the pro-reparative scavenger receptor CD163 on Mon3 was reduced in acute MI (p=0.008), and on other subsets later during the follow-up with lowest levels at day 3 post-MI (p<0.001 for Mon1, p=0.02 for Mon2). CD204 expression on Mon1 correlated with tissue type plasminogen activator levels (r=0.46, p=0.001). Interleukin(IL)6 levels correlated with counts of Mon2-derived CXCR4+ and KDR+ cells. Interleukin-1β correlated with KDR+ Mon2 counts. IL10 correlated with CXCR4+ Mon2 levels. Low count of CXCR4+ Mon2 and low CD163 expression by Mon2 were associated with higher ejection fraction six-weeks after MI. In conclusion, the Mon2 subset has the most prominent role in the observed changes in reparative monocytes in MI. The association of reparative monocytes with inflammatory/fibrinolytic markers indicates a complex interplay of these cells in the post-MI state.Note: The review process for this paper was fully handled by Prof. Christian Weber, Editor in Chief.

Increased expression of cell adhesion molecule receptors on monocyte subsets in ischaemic heart failure

2013 ◽  
Vol 110 (07) ◽  
pp. 92-100 ◽  
Author(s):  
Benjamin Wrigley ◽  
Luke Tapp ◽  
Eduard Shantsila ◽  
Lip Gregory
Keyword(s):  
Heart Failure ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Cox Regression ◽  
Stable Coronary Artery Disease ◽  
Intercellular Adhesion Molecule ◽  
Monocyte Subsets ◽  
Intercellular Adhesion Molecule 1 ◽  
Cox Regression Analysis

SummaryThe objective of this study was to evaluate the expression of cell adhesion molecule (CAM) receptors (integrins) on monocyte subsets in heart failure (HF) and examine their prognostic implication. Increased levels of soluble CAMs have been observed in patients with HF, but the precise mechanism of monocyte adhesion to the vascular endothelium remains unknown. Patients with acute HF (AHF, n=51) were compared to those with stable HF (SHF, n=42) and stable coronary artery disease (CAD, n=44) without HF. Expression of integrins-receptors to intercellular adhesion molecule-1 (ICAM-1R) and vascular CAM-1 (VCAM-1R) on monocyte subsets was assessed by flow cytometry. Monocyte subsets were defined as CD14++CD16–CCR2+ (‘classical’, Mon1), CD14++CD16+CCR2+ (‘intermediate’, Mon2), and CD14+CD16++CCR2– (‘non-classical’, Mon3). Compared to patients with SHF, those with AHF had significantly higher expression of ICAM-1R on Mon2 (p=0.01). Compared to those with stable CAD, patients with SHF had a significantly higher expression of ICAM-1R on Mon2 (p=0.025). Compared to SHF, patients with AHF had a similar expression of VCAM-1R on both Mon1 and Mon3 but significantly higher expression on Mon2 (p=0.019). There were no significant differences between SHF and CAD in monocyte expression of VCAM-1R. In multivariate Cox regression analysis, VCAM-1R expression on Mon2 was associated with adverse clinical outcome (death or rehospitalisation) in AHF [HR 1.07 (1.01–1.14), p=0.029]. In conclusion, HF is associated with increased monocyte expression of integrins-receptors to both ICAM-1 and VCAM-1, being particularly linked to Mon2 subset. Expression of VCAM-1R on Mon2 may have prognostic value in patients with AHF.

Effects of Viola mandshurica on Atherosclerosis and Hepatic Steatosis in ApoE−∕− via the AMPK Pathway

2017 ◽  
Vol 45 (04) ◽  
pp. 757-772 ◽  
Author(s):  
Sun Haeng Park ◽  
Yoon-Young Sung ◽  
Kyoung jin Nho ◽  
Dong Sun Kim ◽  
Ho Kyoung Kim
Keyword(s):  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Inflammatory Responses ◽  
Water Extract ◽  
Intercellular Adhesion Molecule ◽  
Ampk Pathway

Atherosclerosis was previously thought to be a disease that primarily involves lipid accumulation in the arterial wall. In this report, we investigated the effect of Viola mandshurica W. Becker (V. mandshurica) water extract on atherosclerosis in apolipoprotein E deficient (ApoE[Formula: see text]) mice. The administration of V. mandshurica to high-fat diet-fed mice reduced body weight, liver weight, and serum levels of lipids (total cholesterol, low-density lipoprotein-cholesterol, triglycerides), glucose, alanine transaminase, and aspartate transaminase. Histopathologic analyses of the aorta and liver revealed that V. mandshurica attenuated atherosclerotic lesions and reduced lipid accumulation, inflammatory responses and fatty acid synthesis. V. mandshurica also increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), thereby reducing acetyl-CoA carboxylase (ACC) in liver tissue and inhibiting sterol regulatory element-binding protein 1c (SREBP-1c). V. mandshurica reduced protein expression levels of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin) as well as ACC, fatty acid synthase, and SREBP-1c. In addition, quantitative analysis of V. mandshurica by high-performance liquid chromatography revealed the presence of esculetin and scopoletin. Esculetin and scopoletin reduced adhesion molecules in human aortic smooth muscle cells. Our results indicate that the anti-atherosclerotic effects of V. mandshurica may be associated with activation of the AMPK pathway. Therefore, AMPK-dependent phosphorylation of SREBP-1c by V. mandshurica may be an effective therapeutic strategy for combatting atherosclerosis and hepatic steatosis.

scholarly journals High-mannose intercellular adhesion molecule-1 enhances CD16+ monocyte adhesion to the endothelium

2019 ◽  
Vol 317 (5) ◽  
pp. H1028-H1038 ◽  
Author(s):  
Kellie Regal-McDonald ◽  
Brittney Xu ◽  
Jarrod W. Barnes ◽  
Rakesh P. Patel
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Proximity Ligation Assay ◽  
Dependent Manner ◽  
Monocyte Adhesion ◽  
Monocyte Subsets ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
High Mannose

Human monocytes have been classified into three distinct groups, classical (anti-inflammatory; CD14+/CD16−), nonclassical (patrolling; CD14+/CD16++), and intermediate (proinflammatory; CD14++/CD16+). Adhesion of nonclassical/intermediate monocytes with the endothelium is important for innate immunity, and also vascular inflammatory disease. However, there is an incomplete understanding of the mechanisms that regulate CD16+ versus CD16− monocyte adhesion to the inflamed endothelium. Here, we tested the hypothesis that a high-mannose (HM) N-glycoform of intercellular adhesion molecule-1 (ICAM-1) on the endothelium mediates the selective recruitment of CD16+ monocytes. Using TNF-α treatment of human umbilical vein endothelial cells (HUVECs), and using proximity ligation assay for detecting proximity of specific N-glycans and ICAM-1, we show that TNF-α induces HM-ICAM-1 formation on the endothelial surface in a time-dependent manner. We next measured CD16− or CD16+ monocyte rolling and adhesion to TNF-α-treated HUVECs in which HM- or hybrid ICAM-1 N-glycoforms were generated using the α-mannosidase class I and II inhibitors, kifunensine and swainsonine, respectively. Expression of HM-ICAM-1 selectively enhanced CD16+ monocyte adhesion under flow with no effect on CD16− monocytes noted. CD16+ monocyte adhesion was abrogated by blocking either HM epitopes or ICAM-1. A critical role for HM-ICAM-1 in mediating CD16+ monocyte rolling and adhesion was confirmed using COS-1 cells engineered to express HM or complex ICAM-1 N-glycoforms. These data suggest that HM-ICAM-1 selectively recruits nonclassical/intermediate CD16+ monocytes to the activated endothelium. NEW & NOTEWORTHY Monocyte subsets have been associated with cardiovascular disease, yet it is unknown how different subsets are recruited to the endothelium. This study demonstrates the formation of distinct ICAM-1 N-glycoforms in the activated endothelium and reveals a key role for high mannose ICAM-1 in mediating proinflammatory CD16+ monocyte adhesion. Presented data identify roles for endothelial N-glycans in recruiting specific monocyte subsets during inflammation.

Immune complexes alter cerebral microvessel permeability: roles of complement and leukocyte adhesion

2006 ◽  
Vol 291 (2) ◽  
pp. H694-H704 ◽  
Author(s):  
Karyn J. Lister ◽  
Michael J. Hickey
Keyword(s):  
Adhesion Molecule ◽  
Immune Complexes ◽  
Inflammatory Responses ◽  
Leukocyte Adhesion ◽  
Intercellular Adhesion ◽  
Microvascular Permeability ◽  
Intercellular Adhesion Molecule ◽  
Complement Pathway ◽  
Intercellular Adhesion Molecule 1 ◽  
Peripheral Tissues

Immune complexes (ICs) are potent inflammatory mediators in peripheral tissues. However, very few studies have examined the ability of ICs to induce inflammatory responses in the brain. Therefore, using preformed ICs or the reverse passive Arthus (RPA) model to localize ICs to the pial microvasculature of mice, we aimed to investigate the ability of ICs to induce an inflammatory response in the cerebral (pial) microvasculature. Application of preformed ICs immediately increased pial microvascular permeability, with a minimal change in leukocyte adhesion in pial postcapillary venules. In contrast, initiation of the RPA response in the pial microvasculature induced changes in cerebral microvascular permeability and increased leukocyte adhesion in pial postcapillary venules. The RPA response induced deposition of C3 in perivascular regions adjacent to sites of IC formation. Depletion of C3 abrogated RPA-induced microvascular permeability and leukocyte adhesion, indicating that the complement pathway was critical for this response. Inhibition of leukocyte adhesion via CD18 blockade also reduced IC-induced microvascular permeability. However, this did not require intercellular adhesion molecule-1, inasmuch as blockade of intercellular adhesion molecule-1 did not alter RPA-induced microvascular permeability and adhesion. These findings demonstrate that ICs are capable of rapidly inducing inflammatory responses in the cerebral microvasculature, with the complement pathway and leukocyte recruitment playing critical roles in microvascular dysfunction.

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